{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T13:31:43Z","timestamp":1791811903787,"version":"4.3.4"},"reference-count":109,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2020,11,1]],"date-time":"2020-11-01T00:00:00Z","timestamp":1604188800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2020,11,1]],"date-time":"2020-11-01T00:00:00Z","timestamp":1604188800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"funder":[{"DOI":"10.13039\/501100003009","name":"Science and Technology Development Fund","doi-asserted-by":"publisher","award":["0067\/2019\/A2"],"award-info":[{"award-number":["0067\/2019\/A2"]}],"id":[{"id":"10.13039\/501100003009","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Pharmacological Research"],"published-print":{"date-parts":[[2020,11]]},"DOI":"10.1016\/j.phrs.2020.105134","type":"journal-article","created":{"date-parts":[[2020,8,13]],"date-time":"2020-08-13T12:34:13Z","timestamp":1597322053000},"page":"105134","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":24,"special_numbering":"C","title":["The immunomodulatory role of PDEs inhibitors in immune cells: therapeutic implication in rheumatoid arthritis"],"prefix":"10.1016","volume":"161","author":[{"given":"YuFei","family":"He","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yadan","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"ChuTian","family":"Mai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hudan","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hai-Bin","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3223-1797","authenticated-orcid":false,"given":"Ying","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.phrs.2020.105134_bib0005","first-page":"206","article-title":"Genes and Autoimmunity - Intracellular Signaling and Microbiome Contribution","volume":"Vol. 10","author":"W.Brenu","year":"2013"},{"issue":"189","key":"10.1016\/j.phrs.2020.105134_bib0010","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1084\/jem.189.3.587","article-title":"CD8alpha+ and CD8alpha- subclasses of dendritic cells direct the development of distinct T helper cells in vivo","volume":"3","author":"Maldonado-L\u00f3pez","year":"1999","journal-title":"The Journal of experimental medicine"},{"issue":"2","key":"10.1016\/j.phrs.2020.105134_bib0015","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1165\/rcmb.2008-0091TR","article-title":"Cyclic AMP: master regulator of innate immune cell function","volume":"39","author":"Serezani","year":"2008","journal-title":"Am J Respir Cell Mol Biol"},{"key":"10.1016\/j.phrs.2020.105134_bib0020","volume":"7","author":"Raker","year":"2016"},{"issue":"3","key":"10.1016\/j.phrs.2020.105134_bib0025","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1016\/j.pharmthera.2005.07.003","article-title":"Cyclic nucleotide phosphodiesterase (PDE) superfamily: a new target for the development of specific therapeutic agents","volume":"109","author":"Lugnier","year":"2006","journal-title":"Pharmacol Ther"},{"issue":"3","key":"10.1016\/j.phrs.2020.105134_bib0030","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1161\/01.RES.0000256354.95791.f1","article-title":"Overview of PDEs and their regulation","volume":"100","author":"Omori","year":"2007","journal-title":"Circ Res"},{"issue":"3","key":"10.1016\/j.phrs.2020.105134_bib0035","doi-asserted-by":"crossref","first-page":"303","DOI":"10.2174\/1381612820666140826115559","article-title":"Phosphodiesterase: an interface connecting cognitive deficits to neuropsychiatric and neurodegenerative diseases","volume":"21","author":"Wang","year":"2015","journal-title":"Curr Pharm Des"},{"issue":"14","key":"10.1016\/j.phrs.2020.105134_bib0040","doi-asserted-by":"crossref","first-page":"1607","DOI":"10.4155\/fmc.13.127","article-title":"Therapeutic potential of PDE modulation in treating heart disease","volume":"5","author":"Knight","year":"2013","journal-title":"Future Medicinal Chemistry"},{"issue":"5","key":"10.1016\/j.phrs.2020.105134_bib0045","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1067\/mai.2001.119555","article-title":"Cyclic nucleotide phosphodiesterases","volume":"108","author":"Essayan","year":"2001","journal-title":"J Allergy Clin Immunol"},{"issue":"9","key":"10.1016\/j.phrs.2020.105134_bib0050","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1016\/S0006-2952(98)00331-1","article-title":"Cyclic nucleotide phosphodiesterase (PDE) inhibitors and immunomodulation","volume":"57","author":"Essayan","year":"1999","journal-title":"Biochem Pharmacol"},{"issue":"5","key":"10.1016\/j.phrs.2020.105134_bib0055","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1067\/mai.2001.119555","article-title":"Cyclic nucleotide phosphodiesterases","volume":"108","author":"Essayan","year":"2001","journal-title":"Journal of Allergy and Clinical Immunology"},{"issue":"1","key":"10.1016\/j.phrs.2020.105134_bib0060","first-page":"39","article-title":"L. Phosphodiesterase inhibitors as immunomodulatory drugs","volume":"22","author":"Layseca-Espinosa","year":"2003","journal-title":"Inmunologia"},{"issue":"12","key":"10.1016\/j.phrs.2020.105134_bib0065","doi-asserted-by":"crossref","first-page":"1583","DOI":"10.1016\/j.bcp.2012.01.001","article-title":"Apremilast mechanism of action and application to psoriasis and psoriatic arthritis","volume":"83","author":"Schafer","year":"2012","journal-title":"Biochem Pharmacol"},{"issue":"5","key":"10.1016\/j.phrs.2020.105134_bib0070","first-page":"671","article-title":"Molecular mechanisms in allergy and clinical immunology","volume":"108","author":"Gallo","year":"2020","journal-title":"The journal of Allergy and CLinical Immunology"},{"issue":"1","key":"10.1016\/j.phrs.2020.105134_bib0075","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1182\/blood-2002-01-0075","article-title":"Sildenafil and vardenafil, types 5 and 6 phosphodiesterase inhibitors, induce caspase-dependent apoptosis of B-chronic lymphocytic leukemia cells","volume":"101","author":"Sarfati","year":"2003","journal-title":"Blood"},{"issue":"28056","key":"10.1016\/j.phrs.2020.105134_bib0080","first-page":"1","article-title":"Phosphodiesterase 3B (PDE3B) regulates NLRP3 inflammasome in adipose tissue","volume":"6","author":"Ahmad","year":"2016","journal-title":"Scientific Reports"},{"issue":"3","key":"10.1016\/j.phrs.2020.105134_bib0085","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1016\/S0022-3565(25)24562-1","article-title":"Differential regulation of human monocyte-derived TNF alpha and IL-1 beta by type IV cAMP-phosphodiesterase (cAMP-PDE) inhibitors","volume":"272","author":"Verghese","year":"1995","journal-title":"Journal of Pharmacology and Experimental Therapeutics"},{"issue":"5","key":"10.1016\/j.phrs.2020.105134_bib0090","doi-asserted-by":"crossref","first-page":"1529","DOI":"10.1185\/030079908X301866","article-title":"An open-label, single-arm pilot study in patients with severe plaque-type psoriasis treated with an oral anti-inflammatory agent, apremilast","volume":"24","author":"Gottlieb","year":"2008","journal-title":"Current medical research and opinion"},{"issue":"7","key":"10.1016\/j.phrs.2020.105134_bib0095","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1093\/intimm\/dxg079","article-title":"Phosphodiesterase 4 inhibitors reduce human dendritic cell inflammatory cytokine production and Th1-polarizing capacity","volume":"15","author":"Heystek","year":"2003","journal-title":"Int Immunol"},{"issue":"5","key":"10.1016\/j.phrs.2020.105134_bib0100","doi-asserted-by":"crossref","first-page":"1848","DOI":"10.1016\/j.fertnstert.2007.08.043","article-title":"Sildenafil citrate decreased natural killer cell activity and enhanced chance of successful pregnancy in women with a history of recurrent miscarriage","volume":"90","author":"Jerzak","year":"2008","journal-title":"Fertility and sterility"},{"issue":"2","key":"10.1016\/j.phrs.2020.105134_bib0105","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/0898-6568(95)02032-2","article-title":"Rapid regulation of PDE-2 and PDE-4 cyclic AMP phosphodiesterase activity following ligation of the T cell antigen receptor on thymocytes: analysis using the selective inhibitors erythro-9-(2-hydroxy-3-nonyl)-adenine (EHNA) and rolipram","volume":"8","author":"Michie","year":"1996","journal-title":"Cellular signalling"},{"issue":"1\u20132","key":"10.1016\/j.phrs.2020.105134_bib0110","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/S0165-5728(00)00265-4","article-title":"The type IV phosphodiesterase specific inhibitor mesopram inhibits experimental autoimmune encephalomyelitis in rodents","volume":"108","author":"Dinter","year":"2000","journal-title":"Journal of neuroimmunology"},{"key":"10.1016\/j.phrs.2020.105134_bib0115","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.jchemneu.2012.12.005","article-title":"Critical role for PDE4 subfamilies in the development of experimental autoimmune encephalomyelitis","volume":"47","author":"Sanabra","year":"2013","journal-title":"Journal of chemical neuroanatomy"},{"issue":"2","key":"10.1016\/j.phrs.2020.105134_bib0120","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1093\/jnen\/65.2.124","article-title":"Dendritic cells in multiple sclerosis lesions: maturation stage, myelin uptake, and interaction with proliferating T cells","volume":"65","author":"Serafini","year":"2006","journal-title":"Journal of Neuropathology & Experimental Neurology"},{"issue":"3","key":"10.1016\/j.phrs.2020.105134_bib0125","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1111\/bph.12308","article-title":"Comparative assessment of PDE 4 and 7 inhibitors as therapeutic agents in experimental autoimmune encephalomyelitis","volume":"170","author":"Gonzalez-Garcia","year":"2013","journal-title":"Br J Pharmacol"},{"issue":"9","key":"10.1016\/j.phrs.2020.105134_bib0130","doi-asserted-by":"crossref","first-page":"e1326440","DOI":"10.1080\/2162402X.2017.1326440","article-title":"Tadalafil has biologic activity in human melanoma. Results of a pilot trial with Tadalafil in patients with metastatic Melanoma (TaMe)","volume":"6","author":"Hassel","year":"2017","journal-title":"Oncoimmunology"},{"key":"10.1016\/j.phrs.2020.105134_bib0135","doi-asserted-by":"crossref","first-page":"259","DOI":"10.3389\/fphar.2016.00259","article-title":"Differential Expression and Function of PDE8 and PDE4 in Effector T cells: Implications for PDE8 as a Drug Target in Inflammation","volume":"7","author":"Vang","year":"2016","journal-title":"Front Pharmacol"},{"issue":"2","key":"10.1016\/j.phrs.2020.105134_bib0140","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.4049\/jimmunol.164.2.1117","article-title":"Therapeutic potential of phosphodiesterase-4 and-3 inhibitors in Th1-mediated autoimmune diseases","volume":"164","author":"Bielekova","year":"2000","journal-title":"The Journal of Immunology"},{"issue":"26","key":"10.1016\/j.phrs.2020.105134_bib0145","doi-asserted-by":"crossref","first-page":"2016","DOI":"10.1016\/j.cellsig.2014.05.014","article-title":"Apremilast is a selective PDE4 inhibitor with regulatory effects on innate immunity","volume":"9","author":"Schafer","year":"2014","journal-title":"Cellular signalling"},{"issue":"6","key":"10.1016\/j.phrs.2020.105134_bib0150","doi-asserted-by":"crossref","first-page":"1148","DOI":"10.1016\/S1734-1140(10)70377-7","article-title":"Modulating effects of nonselective and selective phosphodiesterase inhibitors on lymphocyte subsets and humoral immune response in mice","volume":"62","author":"Szczypka","year":"2010","journal-title":"Pharmacological Reports"},{"issue":"123","key":"10.1016\/j.phrs.2020.105134_bib0155","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1038\/sj.bjp.0701688","article-title":"Phosphodiesterase profile of human B lymphocytes from normal and atopic donors and the e?ects of PDE inhibition on B cell proliferation","volume":"1998","author":"Gantner","year":"1998","journal-title":"British Journal of Pharmacology"},{"key":"10.1016\/j.phrs.2020.105134_bib0160","first-page":"1","article-title":"Phosphodiesterase 4B negatively regulates endotoxin-activated interleukin-1 receptor antagonist responses in macrophages","volume":"7","author":"Yang","year":"2017","journal-title":"Scientific Reports"},{"issue":"1","key":"10.1016\/j.phrs.2020.105134_bib0165","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1007\/s11481-017-9756-3","article-title":"Mechanisms Involved in the Remyelinating Effect of Sildenafil","volume":"13","author":"D\u00edaz-Lucena","year":"2017","journal-title":"Journal of Neuroimmune Pharmacology"},{"issue":"1727","key":"10.1016\/j.phrs.2020.105134_bib0170","first-page":"1","article-title":"Targeting Phosphodiesterases\u2014Towards a Tailor-Made Approach in Multiple Sclerosis Treatment","volume":"10","author":"Schepers","year":"2019","journal-title":"Frontiers in Immunology"},{"issue":"2","key":"10.1016\/j.phrs.2020.105134_bib0175","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1007\/s00345-012-0848-7","article-title":"Potential therapeutic applications of phosphodiesterase inhibition in prostate cancer","volume":"31","author":"Hamilton","year":"2013","journal-title":"World J Urol"},{"issue":"6","key":"10.1016\/j.phrs.2020.105134_bib0180","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1016\/S0006-2952(99)00188-4","article-title":"Cyclic nucleotide phosphodiesterases (PDE) 3 and 4 in normal, malignant, and HTLV-I transformed human lymphocytes","volume":"58","author":"Ekholm","year":"1999","journal-title":"Biochemical Pharmacology"},{"issue":"6","key":"10.1016\/j.phrs.2020.105134_bib0185","doi-asserted-by":"crossref","first-page":"e1431082","DOI":"10.1080\/2162402X.2018.1431082","article-title":"Phosphodiesterase-5 inhibition reduces postoperative metastatic disease by targeting surgery-induced myeloid derived suppressor cell-dependent inhibition of Natural Killer cell cytotoxicity","volume":"7","author":"Tai","year":"2018","journal-title":"Oncoimmunology"},{"issue":"4","key":"10.1016\/j.phrs.2020.105134_bib0190","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1016\/j.molimm.2013.06.021","article-title":"Gender-specific immunological effects of the phosphodiesterase 5 inhibitor sildenafil in healthy mice","volume":"56","author":"Karakhanova","year":"2013","journal-title":"Molecular immunology"},{"issue":"6","key":"10.1016\/j.phrs.2020.105134_bib0195","doi-asserted-by":"crossref","first-page":"2544","DOI":"10.1210\/en.2011-2120","article-title":"Immune cells have sex and so should journal articles","volume":"153","author":"Klein","year":"2012","journal-title":"Endocrinology"},{"issue":"12","key":"10.1016\/j.phrs.2020.105134_bib0200","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1016\/j.tibs.2006.10.002","article-title":"Epac proteins: multi-purpose cAMP targets","volume":"31","author":"Bos","year":"2006","journal-title":"Trends Biochem Sci"},{"issue":"4","key":"10.1016\/j.phrs.2020.105134_bib0205","first-page":"65","article-title":"Relationship between bcl-2 expression and apoptosis in chicken immune organs including adult and embryo","volume":"22","author":"Zhang","year":"1999","journal-title":"Journal of Nanjing Agricultural University"},{"issue":"12","key":"10.1016\/j.phrs.2020.105134_bib0210","first-page":"1","article-title":"The Regulation of NF-\u03baB Subunits by Phosphorylation","volume":"5","author":"Christian","year":"2016","journal-title":"Cells"},{"issue":"5","key":"10.1016\/j.phrs.2020.105134_bib0215","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1016\/S1097-2765(00)80066-0","article-title":"Phosphorylation of NF-kappa B p65 by PKA stimulates transcriptional activity by promoting a novel bivalent interaction with the coactivator CBP\/p300","volume":"1","author":"Zhong","year":"1998","journal-title":"MOlecular Cell"},{"issue":"6","key":"10.1016\/j.phrs.2020.105134_bib0220","doi-asserted-by":"crossref","first-page":"4712","DOI":"10.1128\/JVI.72.6.4712-4720.1998","article-title":"Inhibition of Phosphodiesterase Type IV Suppresses Human Immunodeficiency Virus Type 1 Replication and Cytokine Production in Primary T Cells: Involvement of NF-\u03baB and NFAT","volume":"72","author":"Navarro","year":"1998","journal-title":"Journal of Virology"},{"issue":"2","key":"10.1016\/j.phrs.2020.105134_bib0225","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1016\/S0022-3565(24)29287-9","article-title":"Phosphodiesterase 4 inhibitors prevent cytokine secretion by T lymphocytes by inhibiting nuclear factor-kappaB and nuclear factor of activated T cells activation","volume":"299","author":"Jimenez","year":"2001","journal-title":"Journal of Pharmacology & Experimental Therapeutics"},{"issue":"1","key":"10.1016\/j.phrs.2020.105134_bib0230","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1097\/00130832-200202000-00010","article-title":"Selective phosphodiesterase inhibitors for the treatment of asthma and chronic obstructive pulmonary disease","volume":"2","author":"Grootendorst","year":"2002","journal-title":"Curr Opin Allergy Clin Immunol"},{"issue":"9454","key":"10.1016\/j.phrs.2020.105134_bib0235","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/S0140-6736(05)17708-3","article-title":"Phosphodiesterase-4 inhibitors for asthma and chronic obstructive pulmonary disease","volume":"365","author":"Lipworth","year":"2005","journal-title":"The Lancet"},{"key":"10.1016\/j.phrs.2020.105134_bib0240","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fimmu.2016.00222","article-title":"Molecular Mechanisms for cAMP-Mediated Immunoregulation in T cells \u2013 Role of Anchored Protein Kinase A Signaling Units","volume":"7","author":"Wehbi","year":"2016","journal-title":"Frontiers in Immunology"},{"key":"10.1016\/j.phrs.2020.105134_bib0245","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.yjmcc.2015.01.015","article-title":"PDE4 inhibition reduces neointima formation and inhibits VCAM-1 expression and histone methylation in an Epac-dependent manner","volume":"81","author":"Lehrke","year":"2015","journal-title":"Journal of Molecular & Cellular Cardiology"},{"issue":"2","key":"10.1016\/j.phrs.2020.105134_bib0250","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1124\/pr.110.003707","article-title":"Exchange protein directly activated by cAMP (epac): a multidomain cAMP mediator in the regulation of diverse biological functions","volume":"65","author":"Schmidt","year":"2013","journal-title":"Pharmacol Rev"},{"issue":"12","key":"10.1016\/j.phrs.2020.105134_bib0255","doi-asserted-by":"crossref","first-page":"1499","DOI":"10.1038\/onc.2014.94","article-title":"Phosphodiesterase 10A: a novel target for selective inhibition of colon tumor cell growth and \u03b2-catenin-dependent TCF transcriptional activity","volume":"34","author":"Li","year":"2015","journal-title":"Oncogene"},{"issue":"2","key":"10.1016\/j.phrs.2020.105134_bib0260","first-page":"97","article-title":"T cell factor 1 regulates Th1\/Th2 cell balance during human immunodeficiency virus infection","volume":"49","author":"Zheng","year":"2020","journal-title":"Journal of China Medical University"},{"issue":"2","key":"10.1016\/j.phrs.2020.105134_bib0265","first-page":"82","article-title":"Overview of researches performed in the laboratory for agrozoology at the Agricultural Faculty of the University of Gent (Belgium)","volume":"473","author":"Chaiso","year":"1989","journal-title":"Biologisch Jaarboek-Dodonaea(Belgium)"},{"issue":"2","key":"10.1016\/j.phrs.2020.105134_bib0270","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.nbd.2010.01.013","article-title":"Sildenafil protects against 3-nitropropionic acid neurotoxicity through the modulation of calpain, CREB, and BDNF","volume":"38","author":"Puerta","year":"2010","journal-title":"Neurobiology of Disease"},{"issue":"2","key":"10.1016\/j.phrs.2020.105134_bib0275","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1002\/jcb.20286","article-title":"Suppression of cyclic GMP-specific phosphodiesterase 5 promotes apoptosis and inhibits growth in HT29 cells","volume":"94","author":"Zhu","year":"2005","journal-title":"Journal of Cellular Biochemistry"},{"key":"10.1016\/j.phrs.2020.105134_bib0280","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1002\/pros.23801","article-title":"Activation of cGMP\/PKG\/p65 signaling associated with PDE5-Is downregulates CCL5 secretion by CD8 <sup>+<\/sup> T cells in benign prostatic hyperplasia","volume":"79","author":"Song","year":"2019","journal-title":"The Prostate"},{"issue":"4","key":"10.1016\/j.phrs.2020.105134_bib0285","doi-asserted-by":"crossref","first-page":"1537","DOI":"10.1182\/blood-2005-07-2901","article-title":"Nitric oxide and cGMP protein kinase (cGK) regulate dendritic-cell migration toward the lymph-node-directing chemokine CCL19","volume":"107","author":"Giordano","year":"2006","journal-title":"Blood"},{"issue":"3","key":"10.1016\/j.phrs.2020.105134_bib0290","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/ar3041","article-title":"Apremilast, a novel PDE4 inhibitor, inhibits spontaneous production of tumour necrosis factor-alpha from human rheumatoid synovial cells and ameliorates experimental arthritis","volume":"12","author":"Mccann","year":"2010","journal-title":"Arthritis research & therapy"},{"issue":"10","key":"10.1016\/j.phrs.2020.105134_bib0295","first-page":"829","article-title":"Effect of selective phosphodiesterase 4 inhibitors on nuclear factor kappa B, tumor necrosis factor-\u03b1 and interleukin-8 expression in peripheral blood mononuclear cells in rheumatoid arthritis with interstitial lung disease","volume":"52","author":"Song","year":"2013","journal-title":"Zhonghua Nei Ke Za Zhi"},{"issue":"14","key":"10.1016\/j.phrs.2020.105134_bib0300","doi-asserted-by":"crossref","first-page":"1255","DOI":"10.2174\/1381612023394665","article-title":"Recent advances in PDE4 inhibitors as immunoregulators and anti-inflammatory drugs","volume":"8","author":"Burnouf","year":"2002","journal-title":"Current pharmaceutical design"},{"issue":"6","key":"10.1016\/j.phrs.2020.105134_bib0305","first-page":"712","article-title":"Current status of selective phosphodiesterase 4 inhibitors in the treatment of rheumatoid arthritis","volume":"28","author":"Xia","year":"2013","journal-title":"Clinical Focus"},{"issue":"4","key":"10.1016\/j.phrs.2020.105134_bib0310","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1038\/nrd4228","article-title":"Advances in targeting cyclic nucleotide phosphodiesterases. Nature reviews","volume":"13","author":"Maurice","year":"2014","journal-title":"Drug discovery"},{"issue":"4","key":"10.1016\/j.phrs.2020.105134_bib0315","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1007\/s40265-017-0709-1","article-title":"Apremilast: A Review in Psoriasis and Psoriatic Arthritis","volume":"77","author":"Keating","year":"2017","journal-title":"Drugs"},{"issue":"8","key":"10.1016\/j.phrs.2020.105134_bib0320","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1007\/s40267-017-0424-8","article-title":"Apremilast in psoriasis: a profile of its use","volume":"33","author":"Deeks","year":"2017","journal-title":"Drugs & Therapy Perspectives"},{"issue":"13","key":"10.1016\/j.phrs.2020.105134_bib0325","doi-asserted-by":"crossref","first-page":"2083","DOI":"10.1517\/14656566.2015.1076794","article-title":"Apremilast for the treatment of psoriasis","volume":"16","author":"Chimenti","year":"2015","journal-title":"Expert Opin Pharmacother"},{"issue":"1","key":"10.1016\/j.phrs.2020.105134_bib0330","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/S1734-1140(12)70744-2","article-title":"Modulation of Th1\/Th2 cytokine production by selective and nonselective phosphodiesterase inhibitors administered to mice","volume":"64","author":"Szczypka","year":"2012","journal-title":"Pharmacological Reports"},{"issue":"2","key":"10.1016\/j.phrs.2020.105134_bib0335","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1165\/ajrcmb.20.2.3140","article-title":"Identification and Function of Cyclic Nucleotide Phosphodiesterase Isoenzymes in Airway Epithelial Cells","volume":"20","author":"Fuhrmann","year":"1999","journal-title":"American Journal of Respiratory Cell & Molecular Biology"},{"issue":"12","key":"10.1016\/j.phrs.2020.105134_bib0340","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1371\/journal.pone.0082509","article-title":"Inhibitory Effects of Vinpocetine on the Progression of Atherosclerosis Are Mediated by Akt\/NF-\u03baB Dependent Mechanisms in apoE-\/- Mice","volume":"8","author":"Zhuang","year":"2013","journal-title":"Plos One"},{"key":"10.1016\/j.phrs.2020.105134_bib0345","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1124\/pr.58.3.5","article-title":"Cyclic Nucleotide Phosphodiesterases: Molecular Regulation to Clinical Use","volume":"58","author":"Bender","year":"2006","journal-title":"Pharmacological reviews"},{"key":"10.1016\/j.phrs.2020.105134_bib0350","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1016\/j.lfs.2012.07.003","article-title":"Efficacy of concurrent administration of cilostazol and methotrexate in rheumatoid arthritis: pharmacologic and clinical significance","volume":"91","author":"Kim","year":"2012","journal-title":"Life sciences"},{"issue":"3","key":"10.1016\/j.phrs.2020.105134_bib0355","first-page":"635","article-title":"Effect of phosphodiesterase-5 inhibition on joint and muscle damage in rats with adjuvant arthritis","volume":"48","author":"Bahadir","year":"2018","journal-title":"Turk J Med Sci"},{"issue":"2","key":"10.1016\/j.phrs.2020.105134_bib0360","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1007\/s11095-019-2727-z","article-title":"Comparative Assessment of the New PDE7 Inhibitor - GRMS-55 and Lisofylline in Animal Models of Immune-Related Disorders: A PK\/PD Modeling Approach","volume":"37","author":"Swierczek","year":"2020","journal-title":"Pharm Res"},{"issue":"2\u20133","key":"10.1016\/j.phrs.2020.105134_bib0365","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/j.ejphar.2006.11.079","article-title":"Amelioration of collagen-induced arthritis in mice by a novel phosphodiesterase 7 and 4 dual inhibitor, YM-393059","volume":"559","author":"Yamamoto","year":"2007","journal-title":"Eur J Pharmacol"},{"issue":"2","key":"10.1016\/j.phrs.2020.105134_bib0370","doi-asserted-by":"crossref","first-page":"854","DOI":"10.1016\/j.intimp.2015.08.031","article-title":"Protective role of theophylline and their interaction with nitric oxide (NO) in adjuvant-induced rheumatoid arthritis in rats","volume":"29","author":"Pal","year":"2015","journal-title":"Int Immunopharmacol"},{"issue":"3","key":"10.1016\/j.phrs.2020.105134_bib0375","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/S0898-6568(01)00250-9","article-title":"PDE7A is expressed in human B-lymphocytes and is up-regulated by elevation of intracellular cAMP","volume":"14","author":"Lee","year":"2002","journal-title":"Cellular Signalling"},{"issue":"6","key":"10.1016\/j.phrs.2020.105134_bib0380","doi-asserted-by":"crossref","first-page":"1679","DOI":"10.1124\/mol.104.002246","article-title":"Discovery of BRL 50481 [3-(N,N-dimethylsulfonamido)-4-methyl-nitrobenzene], a Selective Inhibitor of Phosphodiesterase 7: In Vitro Studies in Human Monocytes, Lung Macrophages, and CD8+ T-Lymphocytes","volume":"66","author":"Smith","year":"2004","journal-title":"Molecular Pharmacology"},{"issue":"18","key":"10.1016\/j.phrs.2020.105134_bib0385","doi-asserted-by":"crossref","first-page":"4615","DOI":"10.1016\/j.bmcl.2004.07.009","article-title":"Discovery of thiadiazoles as a novel structural class of potent and selective PDE7 inhibitors. Part 2: metabolism-directed optimization studies towards orally bioavailable derivatives","volume":"14","author":"F, V","year":"2004","journal-title":"Bioorganic and Medicinal Chemistry Letters"},{"issue":"2","key":"10.1016\/j.phrs.2020.105134_bib0390","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.imlet.2009.01.004","article-title":"ASB16165, a novel inhibitor for phosphodiesterase 7A (PDE7A), suppresses IL-12-induced IFN-gamma production by mouse activated T lymphocytes","volume":"122","author":"Kumiko","year":"2009","journal-title":"Immunology letters"},{"issue":"12","key":"10.1016\/j.phrs.2020.105134_bib0395","doi-asserted-by":"crossref","first-page":"6253","DOI":"10.4049\/jimmunol.159.12.6253","article-title":"Suppression of TNF-alpha expression, inhibition of Th1 activity, and amelioration of collagen-induced arthritis by rolipram","volume":"159","author":"Ross","year":"1997","journal-title":"Journal of Immunology"},{"issue":"1","key":"10.1016\/j.phrs.2020.105134_bib0400","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1186\/s12974-019-1649-3","article-title":"The phosphodiesterase 10 inhibitor papaverine exerts anti-inflammatory and neuroprotective effects via the PKA signaling pathway in neuroinflammation and Parkinson\u2019s disease mouse models","volume":"16","author":"Lee","year":"2019","journal-title":"Journal of neuroinflammation"},{"issue":"5","key":"10.1016\/j.phrs.2020.105134_bib0405","doi-asserted-by":"crossref","first-page":"3715","DOI":"10.3892\/mmr.2016.5005","article-title":"The cyclic AMP signaling pathway: Exploring targets for successful drug discovery","volume":"13","author":"Yan","year":"2016","journal-title":"Mol Med Rep"},{"issue":"7","key":"10.1016\/j.phrs.2020.105134_bib0410","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1016\/j.cellsig.2016.01.008","article-title":"Location, location, location: PDE4D5 function is directed by its unique N-terminal region","volume":"28","author":"Wills","year":"2016","journal-title":"Cell Signal"},{"issue":"10","key":"10.1016\/j.phrs.2020.105134_bib0415","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1038\/s41573-019-0033-4","article-title":"Therapeutic targeting of 3',5'-cyclic nucleotide phosphodiesterases: inhibition and beyond","volume":"18","author":"Baillie","year":"2019","journal-title":"Nat Rev Drug Discov"},{"issue":"4","key":"10.1016\/j.phrs.2020.105134_bib0420","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/j.annder.2018.03.001","article-title":"Apremilast withdrawals more frequent in standard practice than in clinical trials","volume":"145","author":"Schmutz","year":"2018","journal-title":"Annales de Dermatologie et de V\u00e9n\u00e9r\u00e9ologie"},{"issue":"10","key":"10.1016\/j.phrs.2020.105134_bib0425","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1038\/ncb3405","article-title":"Interaction between integrin \u03b15 and PDE4D regulates endothelial inflammatory signalling","volume":"18","author":"Yun","year":"2016","journal-title":"Nat Cell Biol"},{"issue":"11","key":"10.1016\/j.phrs.2020.105134_bib0430","doi-asserted-by":"crossref","first-page":"6763","DOI":"10.1074\/jbc.M115.638585","article-title":"Regulation of sarcoplasmic reticulum Ca2+ ATPase 2 (SERCA2) activity by phosphodiesterase 3A (PDE3A) in human myocardium: phosphorylation-dependent interaction of PDE3A1 with SERCA2","volume":"290","author":"Ahmad","year":"2015","journal-title":"J Biol Chem"},{"issue":"4","key":"10.1016\/j.phrs.2020.105134_bib0435","doi-asserted-by":"crossref","first-page":"1080","DOI":"10.1038\/npp.2015.240","article-title":"Specific Inhibition of Phosphodiesterase-4B Results in Anxiolysis and Facilitates Memory Acquisition","volume":"41","author":"McGirr","year":"2016","journal-title":"Neuropsychopharmacology"},{"issue":"2","key":"10.1016\/j.phrs.2020.105134_bib0440","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1093\/biostatistics\/kxx069","article-title":"Estimation of clinical trial success rates and related parameters","volume":"20","author":"Wong","year":"2019","journal-title":"Biostatistics"},{"issue":"12","key":"10.1016\/j.phrs.2020.105134_bib0445","doi-asserted-by":"crossref","first-page":"1803","DOI":"10.1007\/s00213-017-4587-8","article-title":"Phosphodiesterase-1b (Pde1b) knockout mice are resistant to forced swim and tail suspension induced immobility and show upregulation of Pde10a","volume":"234","author":"Hufgard","year":"2017","journal-title":"Psychopharmacology (Berl)"},{"issue":"0","key":"10.1016\/j.phrs.2020.105134_bib0450","first-page":"137","article-title":"Ibudilast: a nonselective phosphodiesterase inhibitor in brain disorders","volume":"71","author":"Schwenkgrub","year":"2017","journal-title":"Postepy Hig Med Dosw (Online)"},{"issue":"9","key":"10.1016\/j.phrs.2020.105134_bib0455","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1056\/NEJMoa1803583","article-title":"Phase 2 Trial of Ibudilast in Progressive Multiple Sclerosis","volume":"379","author":"Fox","year":"2018","journal-title":"The New England journal of medicine"},{"issue":"9","key":"10.1016\/j.phrs.2020.105134_bib0460","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1016\/S2213-2600(13)70187-5","article-title":"Efficacy and safety of RPL554, a dual PDE3 and PDE4 inhibitor, in healthy volunteers and in patients with asthma or chronic obstructive pulmonary disease: findings from four clinical trials","volume":"1","author":"Franciosi","year":"2013","journal-title":"Lancet Respiratory Medicine"},{"issue":"3","key":"10.1016\/j.phrs.2020.105134_bib0465","doi-asserted-by":"crossref","first-page":"725","DOI":"10.3390\/ph3030725","article-title":"Theophylline","volume":"3","author":"Barnes","year":"2010","journal-title":"Pharmaceuticals (Basel, Switzerland)"},{"issue":"7","key":"10.1016\/j.phrs.2020.105134_bib0470","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1164\/rccm.200906-0937OC","article-title":"Targeting phosphoinositide-3-kinase-delta with theophylline reverses corticosteroid insensitivity in chronic obstructive pulmonary disease","volume":"182","author":"To","year":"2010","journal-title":"Am J Respir Crit Care Med"},{"issue":"4","key":"10.1016\/j.phrs.2020.105134_bib0475","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.jccase.2016.12.004","article-title":"A case of life-threatening supraventricular tachycardia storm associated with theophylline toxicity","volume":"15","author":"Ichikawa","year":"2017","journal-title":"Journal of Cardiology Cases"},{"issue":"2","key":"10.1016\/j.phrs.2020.105134_bib0480","doi-asserted-by":"crossref","first-page":"267","DOI":"10.2332\/allergolint.08-OA-0053","article-title":"Effects of KF19514, a phosphodiesterase 4 and 1 Inhibitor, on bronchial inflammation and remodeling in a murine model of chronic asthma","volume":"58","author":"Kita","year":"2009","journal-title":"Allergol Int"},{"issue":"4","key":"10.1016\/j.phrs.2020.105134_bib0485","doi-asserted-by":"crossref","first-page":"421","DOI":"10.2174\/156802607779941224","article-title":"Re-discovering PDE3 inhibitors--new opportunities for a long neglected target","volume":"7","author":"Thompson","year":"2007","journal-title":"Curr Top Med Chem"},{"key":"10.1016\/j.phrs.2020.105134_bib0490","first-page":"415","article-title":"Harnessing the clinical efficacy of phosphodiesterase 4 inhibitors in inflammatory lung diseases: dual-selective phosphodiesterase inhibitors and novel combination therapies","volume":"Vol. 204","author":"Giembycz","year":"2011"},{"issue":"3","key":"10.1016\/j.phrs.2020.105134_bib0495","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1016\/j.coph.2012.02.019","article-title":"New bronchodilators","volume":"12","author":"Mak","year":"2012","journal-title":"Curr Opin Pharmacol"},{"issue":"5","key":"10.1016\/j.phrs.2020.105134_bib0500","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1002\/cmdc.200900043","article-title":"Synthesis, Structural Analysis, and Biological Evaluation of Thioxoquinazoline Derivatives as Phosphodiesterase 7 Inhibitors","volume":"4","author":"Casta\u00f1o","year":"2009","journal-title":"ChemMedChem"},{"issue":"3","key":"10.1016\/j.phrs.2020.105134_bib0505","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/j.coph.2012.02.016","article-title":"Selective PDE inhibitors as novel treatments for respiratory diseases","volume":"12","author":"Page","year":"2012","journal-title":"Curr Opin Pharmacol"},{"issue":"3","key":"10.1016\/j.phrs.2020.105134_bib0510","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1124\/jpet.113.204644","article-title":"Effect of the mixed phosphodiesterase 3\/4 inhibitor RPL554 on human isolated bronchial smooth muscle tone","volume":"346","author":"Calzetta","year":"2013","journal-title":"J Pharmacol Exp Ther"},{"issue":"1\u20133","key":"10.1016\/j.phrs.2020.105134_bib0515","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.ejphar.2005.12.059","article-title":"Phosphodiesterase inhibitors in airways disease","volume":"533","author":"Fan Chung","year":"2006","journal-title":"Eur J Pharmacol"},{"key":"10.1016\/j.phrs.2020.105134_bib0520","doi-asserted-by":"crossref","first-page":"123","DOI":"10.3389\/fimmu.2016.00123","article-title":"The cAMP Pathway as Therapeutic Target in Autoimmune and Inflammatory Diseases","volume":"7","author":"Raker","year":"2016","journal-title":"Front Immunol"},{"issue":"6","key":"10.1016\/j.phrs.2020.105134_bib0525","first-page":"304","article-title":"Prostaglandins and chronic inflammation","volume":"33","author":"Aoki","year":"2012","journal-title":"Agents & Actions Supplements"},{"issue":"8","key":"10.1016\/j.phrs.2020.105134_bib0530","doi-asserted-by":"crossref","first-page":"91","DOI":"10.3109\/03009747909105343","article-title":"Cyclic nucleotides in joint fluid in rheumatoid arthritis and in Reiter\u2019s syndrome","volume":"2","author":"Trang","year":"1979","journal-title":"Scandinavian journal of rheumatology"},{"issue":"9","key":"10.1016\/j.phrs.2020.105134_bib0535","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1056\/NEJMoa1803583","article-title":"Phase 2 Trial of Ibudilast in Progressive Multiple Sclerosis","volume":"379","author":"Fox","year":"2018","journal-title":"N Engl J Med"},{"issue":"9","key":"10.1016\/j.phrs.2020.105134_bib0540","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1016\/S2213-2600(13)70187-5","article-title":"Efficacy and safety of RPL554, a dual PDE3 and PDE4 inhibitor, in healthy volunteers and in patients with asthma or chronic obstructive pulmonary disease: findings from four clinical trials","volume":"1","author":"Franciosi","year":"2013","journal-title":"Lancet Respir Med"},{"issue":"5","key":"10.1016\/j.phrs.2020.105134_bib0545","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1002\/cmdc.200900043","article-title":"Synthesis, structural analysis, and biological evaluation of thioxoquinazoline derivatives as phosphodiesterase 7 inhibitors","volume":"4","author":"Castano","year":"2009","journal-title":"ChemMedChem"}],"container-title":["Pharmacological Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1043661820314420?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1043661820314420?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,19]],"date-time":"2025-10-19T22:13:35Z","timestamp":1760912015000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1043661820314420"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11]]},"references-count":109,"alternative-id":["S1043661820314420"],"URL":"https:\/\/doi.org\/10.1016\/j.phrs.2020.105134","relation":{},"ISSN":["1043-6618"],"issn-type":[{"value":"1043-6618","type":"print"}],"subject":[],"published":{"date-parts":[[2020,11]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"The immunomodulatory role of PDEs inhibitors in immune cells: therapeutic implication in rheumatoid arthritis","name":"articletitle","label":"Article Title"},{"value":"Pharmacological Research","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.phrs.2020.105134","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2020 Elsevier Ltd. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"105134"}}