{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T23:12:23Z","timestamp":1772752343980,"version":"3.50.1"},"reference-count":42,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,7,20]],"date-time":"2021-07-20T00:00:00Z","timestamp":1626739200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Kaohsiung Chang Gung Memorial Hospital, Taiwan","award":["CMRPG8G0791, CMRPG8G0792, CMRPG8G1501"],"award-info":[{"award-number":["CMRPG8G0791, CMRPG8G0792, CMRPG8G1501"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Janus kinase 2 (JAK2) is a member of the JAK family that transduces cytokine-mediated signals via the JAKs\/STATs (signal transducer and activator of transcription proteins) pathway, which plays an important role in many inflammatory diseases. This study investigates the association of p-JAK2 and JAK2-associated cytokines from nasal polyp (NP) tissue with disease severity, and evaluates the p-JAK2-mediated STATs in chronic rhinosinusitis (CRS) with NP. Sixty-one CRSwNP patients with nasal polyps undergoing endoscopic sinus surgery were enrolled, while the turbinate tissues from 26 nasal obstruction patients were examined as the control group. Elevated levels of p-JAK2 were detected in CRSwNP, and significantly correlated with scores of disease severity (LMK-CT, TPS, and SNOT-22). Expressions of the JAK2-associated cytokines, such as IL-5, IL-6, IL-13, G-CSF, and IFN-\u03b3 were significantly higher in CRSwNP than in the controls, while the levels of IL-5, IL-6, IL-13, or G-CSF had positive correlation with scores of disease severity. Moreover, markedly increased expression of p-STAT3 in CRSwNP was observed relative to the control. Taken together, these data showed that the JAK2-associated cytokines including IL-6 and G-CSF may stimulate JAK2 phosphorylation to activate p-STAT3, indicating an association with disease severity and supporting its development of JAK2 inhibitor as a potential therapeutic agent for CRS.<\/jats:p>","DOI":"10.3390\/biom11071059","type":"journal-article","created":{"date-parts":[[2021,7,20]],"date-time":"2021-07-20T05:10:59Z","timestamp":1626757859000},"page":"1059","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["JAK2 Phosphorylation Signals and Their Associated Cytokines Involved in Chronic Rhinosinusitis with Nasal Polyps and Correlated with Disease Severity"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7311-8638","authenticated-orcid":false,"given":"Yu-Tsai","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Otolaryngology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University, College of Medicine, Kaohsiung 833, Taiwan"},{"name":"Kaohsiung Chang Gung Head and Neck Oncology Group, Cancer Center, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan"},{"name":"College of Pharmacy and Health Care, Tajen University, Pingtung County 907, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4124-0222","authenticated-orcid":false,"given":"Wei-Chih","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University, College of Medicine, Kaohsiung 833, Taiwan"},{"name":"Kaohsiung Chang Gung Head and Neck Oncology Group, Cancer Center, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6877-1579","authenticated-orcid":false,"given":"Ming-Hsien","family":"Tsai","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University, College of Medicine, Kaohsiung 833, Taiwan"},{"name":"Kaohsiung Chang Gung Head and Neck Oncology Group, Cancer Center, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan"},{"name":"College of Pharmacy and Health Care, Tajen University, Pingtung County 907, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing-Ying","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pathology and Lab Medicine, Kaohsiung Veterans General Hospital, Kaohsiung 813, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6690-6038","authenticated-orcid":false,"given":"Chih-Yen","family":"Chien","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University, College of Medicine, Kaohsiung 833, Taiwan"},{"name":"Kaohsiung Chang Gung Head and Neck Oncology Group, Cancer Center, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shun-Chen","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Anatomic Pathology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University, Kaohsiung 833, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,20]]},"reference":[{"key":"ref_1","first-page":"S1","article-title":"Clinical practice guideline (update): Adult sinusitis. Otolaryngol","volume":"152","author":"Rosenfeld","year":"2015","journal-title":"Head. Neck. Surg."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4193\/Rhin20.401","article-title":"EPOS 2020: European position paper on rhinosinusitis and nasal polyps 2020","volume":"58","author":"Fokkens","year":"2020","journal-title":"Rhinology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.1002\/lary.25180","article-title":"Cost of adult chronic rhinosinusitis: A systematic review","volume":"125","author":"Smith","year":"2015","journal-title":"Laryngoscope"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1459","DOI":"10.1111\/all.13411","article-title":"Multidimensional endotypes of chronic rhinosinusitis and their association with treatment outcomes","volume":"73","author":"Liao","year":"2018","journal-title":"Allergy"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1023\/A:1023494025748","article-title":"Quality of Life in Taiwanese Adults with Chronic Rhino-Sinusitis","volume":"12","author":"Wang","year":"2003","journal-title":"Qual. Life. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1124\/pr.116.012518","article-title":"Kinases as Novel Therapeutic Targets in Asthma and Chronic Obstructive Pulmonary Disease","volume":"68","author":"Barnes","year":"2016","journal-title":"Pharmacol. Rev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1279","DOI":"10.1172\/JCI0215786","article-title":"JAK-STAT signaling in asthma","volume":"109","author":"Pernis","year":"2002","journal-title":"J. Clin. Investig."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"6237","DOI":"10.4049\/jimmunol.179.9.6237","article-title":"The role of IkappaB kinase 2, but not activation of NF-kappaB, in the release of CXCR3 ligands from IFN-\u03b3-stimulated human bronchial epithelial cells","volume":"179","author":"Tudhope","year":"2007","journal-title":"J. Immunol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1183\/09031936.04.00080303","article-title":"STAT4 activation in smokers and patients with chronic obstructive pulmonary disease","volume":"24","author":"Caramori","year":"2004","journal-title":"Eur. Respir. J."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1183\/09031936.00228414","article-title":"JAK-STAT pathway activation in COPD","volume":"46","author":"Birrell","year":"2015","journal-title":"Eur. Respir. J."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"182","DOI":"10.2500\/ajra.2015.29.4170","article-title":"Increased phosphorylation of STAT5b, but not STAT5a, in nasal polyps","volume":"29","author":"Linke","year":"2015","journal-title":"Am. J. Rhinol. Allergy"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1757","DOI":"10.2147\/DDDT.S243053","article-title":"Dupilumab: Clinical efficacy of blocking IL-4\/IL-13 signalling in chronic rhinosinusitis with nasal polyps","volume":"14","author":"Kariyawasam","year":"2020","journal-title":"Drug Des. Devel. Ther."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1016\/j.jaci.2008.07.008","article-title":"Different types of T effector cells orchestrate mucosal inflammation in chronic sinus disease","volume":"122","author":"Zhang","year":"2008","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2343","DOI":"10.1007\/s00405-012-1927-5","article-title":"Plasma RANTES and eotaxin levels are correlated with the severity of chronic rhinosinusitis","volume":"269","author":"Chao","year":"2012","journal-title":"Eur. Arch. Otorhinolaryngol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1230","DOI":"10.1016\/j.jaci.2017.09.009","article-title":"Chronic rhinosinusitis in Asia","volume":"140","author":"Zhang","year":"2017","journal-title":"J. Allergy. Clin. Immunol."},{"key":"ref_16","first-page":"17","article-title":"Quantification for staging sinusitis. International Conference on Sinus Disease: Terminology, Staging, Therapy. Ann. Otol","volume":"104","author":"Lund","year":"1995","journal-title":"Rhinol. Laryngol. Suppl."},{"key":"ref_17","first-page":"183","article-title":"Staging in rhinosinusitus","volume":"31","author":"Lund","year":"1993","journal-title":"Rhinology"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"S17","DOI":"10.1016\/j.jaci.2006.09.005","article-title":"Rhinosinusitis: Developing guidance for clinical trials","volume":"118","author":"Meltzer","year":"2006","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.jaci.2012.07.047","article-title":"Omalizumab is effective in allergic and nonallergic patients with nasal polyps and asthma","volume":"131","author":"Gevaert","year":"2013","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1111\/j.1749-4486.2009.01995.x","article-title":"Psychometric validity of the 22-item Sinonasal Outcome Test","volume":"34","author":"Hopkins","year":"2009","journal-title":"Clin. Otolaryngol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1016\/j.jaci.2011.07.049","article-title":"Pathogenesis of chronic rhinosinusitis: Inflammation","volume":"128","author":"VanCrombruggen","year":"2011","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1146\/annurev.immunol.17.1.255","article-title":"Immunologic basis of antigen-induced airway hyperresponsiveness","volume":"17","year":"1999","journal-title":"Annu. Rev. Immunol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"6409","DOI":"10.4049\/jimmunol.173.10.6409","article-title":"IL-5 and granulocyte-macrophage colony-stimulating factor activate STAT3 and STAT5 and promote Pim-1 and cyclin D3 protein expression in human eosinophils","volume":"173","author":"Stout","year":"2004","journal-title":"J. Immunol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"L627","DOI":"10.1152\/ajplung.00285.2011","article-title":"Deregulated Stat3 signaling dissociates pulmonary inflammation from emphysema in gp130 mutant mice","volume":"302","author":"Ruwanpura","year":"2012","journal-title":"Am. J. Physiol. Lung. Cell. Mol. Physiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.freeradbiomed.2012.10.553","article-title":"IL-4 and IL-13 employ discrete signaling pathways for target gene expression in alternatively activated monocytes\/macrophages","volume":"54","author":"Bhattacharjee","year":"2013","journal-title":"Free. Radic. Biol. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1038\/382171a0","article-title":"Requirement for Stat4 in interleukin-12- mediated responses of natural killer and T cells","volume":"382","author":"Thierfelder","year":"1996","journal-title":"Nature"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"4053","DOI":"10.4049\/jimmunol.162.7.4053","article-title":"Repression of IL-4-induced gene expression by IFN-gammarequires Stat1 activation","volume":"162","author":"Venkataraman","year":"1999","journal-title":"J. Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1016\/j.immuni.2015.08.010","article-title":"The Cytokine GM-CSF drives the inflammatory signature of CCR2+ monocytes and licenses qutoimmunity","volume":"43","author":"Croxford","year":"2015","journal-title":"Immunity"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1016\/j.immuni.2016.10.026","article-title":"GM-CSF: From growth factor to central mediator of tissue inflammation","volume":"45","author":"Becher","year":"2016","journal-title":"Immunity"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2406","DOI":"10.1172\/JCI98224","article-title":"Granulocyte-CSF links destructive inflammation and comorbidities in obstructive lung disease","volume":"128","author":"Tsantikos","year":"2018","journal-title":"J. Clin. Investig"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1512","DOI":"10.1002\/jcb.21542","article-title":"The granulocyte colony stimulating factor (G-CSF) activates JAK\/STAT and MAPK pathways in a trophoblastic cell line","volume":"103","author":"Marino","year":"2008","journal-title":"J. Cell Biochem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/S1074-7613(01)00101-7","article-title":"STAT-3 activation is required for normal G-CSF-dependent proliferation and granulocytic differentiation","volume":"14","author":"McLemore","year":"2001","journal-title":"Immunity"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"50s","DOI":"10.1183\/09031936.01.00229701","article-title":"Cytokines in chronic obstructive pulmonary disease","volume":"34","author":"Chung","year":"2001","journal-title":"Eur. Respir. J. Suppl."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/s13223-016-0123-3","article-title":"Cytokine patterns in nasal secretion of non-atopic patients distinguish between chronic rhinosinusitis with or without nasal polys","volume":"12","author":"Klemens","year":"2016","journal-title":"Allergy Asthma. Clin. Immunol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/j.jaci.2009.10.072","article-title":"Evidence for altered activity of the IL-6 pathway in chronic rhinosinusitis with nasal polyps","volume":"125","author":"Peters","year":"2010","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1159\/000353893","article-title":"Increased Activation and Differentiated Localization of Native and Phosphorylated STAT3 in Nasal Polyps","volume":"162","author":"Linke","year":"2013","journal-title":"Int. Arch. Allergy Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1682","DOI":"10.3389\/fimmu.2019.01682","article-title":"IL-19 Up-Regulates Mucin 5AC Production in Patients With Chronic Rhinosinusitis via STAT3 Pathway","volume":"10","author":"Lai","year":"2019","journal-title":"Front Immunol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1007\/s11882-011-0189-4","article-title":"Genetics of rhinosinusitis","volume":"11","author":"Zhang","year":"2011","journal-title":"Curr. Allergy. Asthma. Rep."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"111","DOI":"10.2500\/ajr.2008.22.3135","article-title":"Allergic profiles in unilateral nasal polyps of bilateral chronic rhinosinusitis","volume":"22","author":"Li","year":"2008","journal-title":"Am. J. Rhinol."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Lee, T.J., Fu, C.H., Wang, C.H., Huang, C.C., Huang, C.C., Chang, P.H., Chen, Y.W., Wu, C.C., Wu, C.L., and Kuo, H.P. (2017). Impact of chronic rhinosinusitis on severe asthma patients. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0171047"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e5432","DOI":"10.1097\/MD.0000000000005432","article-title":"Association between cigarette smoking and interleukin-17A expression in nasal tissues of patients with chronic rhinosinusitis and asthma","volume":"95","author":"Huang","year":"2016","journal-title":"Medicine"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1007\/s40265-017-0736-y","article-title":"Erratum to: JAK-STAT Signaling as a Target for Inflammatory and Autoimmune Diseases: Current and Future Prospects","volume":"77","author":"Banerjee","year":"2017","journal-title":"Drugs"}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/11\/7\/1059\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:32:09Z","timestamp":1760164329000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/11\/7\/1059"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,20]]},"references-count":42,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2021,7]]}},"alternative-id":["biom11071059"],"URL":"https:\/\/doi.org\/10.3390\/biom11071059","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,20]]}}}