{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,25]],"date-time":"2025-10-25T19:11:07Z","timestamp":1761419467216,"version":"build-2065373602"},"reference-count":93,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,6,22]],"date-time":"2021-06-22T00:00:00Z","timestamp":1624320000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Funda\u00e7\u00e3o de Amparo a Pesquisa do Estado de Sao Paulo","award":["2015\/50040-4"],"award-info":[{"award-number":["2015\/50040-4"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Matrix metalloproteinases (MMPs) are proteolytic enzymes that have been associated with the pathogenesis of inflammatory diseases and obesity. Adipose tissue in turn is an active endocrine organ capable of secreting a range of proinflammatory mediators with autocrine and paracrine properties, which contribute to the inflammation of adipose tissue and adjacent tissues. However, the potential inflammatory effects of MMPs in adipose tissue cells are still unknown. This study investigates the effects of BmooMP\u03b1-I, a single-domain snake venom metalloproteinase (SVMP), in activating an inflammatory response by 3T3-L1 preadipocytes in culture, focusing on prostaglandins (PGs), cytokines, and adipocytokines biosynthesis and mechanisms involved in prostaglandin E2 (PGE2) release. The results show that BmooMP\u03b1-I induced the release of PGE2, prostaglandin I2 (PGI2), monocyte chemoattractant protein-1 (MCP-1), and adiponectin by preadipocytes. BmooMP\u03b1-I-induced PGE2 biosynthesis was dependent on group-IIA-secreted phospholipase A2 (sPLA2-IIA), cytosolic phospholipase A2-\u03b1 (cPLA2-\u03b1), and cyclooxygenase (COX)-1 and -2 pathways. Moreover, BmooMP\u03b1-I upregulated COX-2 protein expression but not microsomal prostaglandin E synthase-1 (mPGES-1) expression. In addition, we demonstrate that the enzymatic activity of BmooMP\u03b1-I is essential for the activation of prostanoid synthesis pathways in preadipocytes. These data highlight preadipocytes as important targets for metalloproteinases and provide new insights into the contribution of these enzymes to the inflammation of adipose tissue and tissues adjacent to it.<\/jats:p>","DOI":"10.3390\/biom11070921","type":"journal-article","created":{"date-parts":[[2021,6,22]],"date-time":"2021-06-22T13:02:10Z","timestamp":1624366930000},"page":"921","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["A Metalloproteinase Induces an Inflammatory Response in Preadipocytes with the Activation of COX Signalling Pathways and Participation of Endogenous Phospholipases A2"],"prefix":"10.3390","volume":"11","author":[{"given":"Priscila Motta","family":"Janovits","sequence":"first","affiliation":[{"name":"Laborat\u00f3rio de Farmacologia, Instituto Butantan, S\u00e3o Paulo 05503-900, Brazil"},{"name":"Centre of Excellence in New Target Discovery (CENTD), Instituto Butantan, S\u00e3o Paulo 05503-900, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elbio","family":"Leiguez","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Farmacologia, Instituto Butantan, S\u00e3o Paulo 05503-900, Brazil"},{"name":"Centre of Excellence in New Target Discovery (CENTD), Instituto Butantan, S\u00e3o Paulo 05503-900, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Viviane","family":"Portas","sequence":"additional","affiliation":[{"name":"Centre of Excellence in New Target Discovery (CENTD), Instituto Butantan, S\u00e3o Paulo 05503-900, Brazil"},{"name":"Laborat\u00f3rio de Desenvolvimento e Inova\u00e7\u00e3o, Instituto Butantan, S\u00e3o Paulo 05503-900, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5887-7663","authenticated-orcid":false,"given":"Catarina","family":"Teixeira","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Farmacologia, Instituto Butantan, S\u00e3o Paulo 05503-900, Brazil"},{"name":"Centre of Excellence in New Target Discovery (CENTD), Instituto Butantan, S\u00e3o Paulo 05503-900, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2571","DOI":"10.1016\/j.bbagen.2014.03.007","article-title":"Matrix metalloproteinases in inflammation","volume":"1840","author":"Nissinen","year":"2014","journal-title":"Biochim. Biophys. Acta Gen. Subj."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/bs.pmbts.2017.02.005","article-title":"Biochemical and Biological Attributes of Matrix Metalloproteinases","volume":"147","author":"Cui","year":"2017","journal-title":"Prog. Mol. Biol. Transl. Sci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2036","DOI":"10.1016\/j.bbamcr.2017.05.010","article-title":"Matrix metalloproteinases as regulators of inflammatory processes","volume":"1864","author":"Fingleton","year":"2017","journal-title":"Biochim. Biophys. Acta Mol. Cell Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2145","DOI":"10.1096\/fasebj.5.8.1850705","article-title":"Matrix metalloproteinases and their inhibitors in connective tissue remodeling","volume":"5","author":"Woessner","year":"1991","journal-title":"FASEB J."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"49","DOI":"10.5603\/EP.a2018.0067","article-title":"The association between serum metalloproteinase concentration, obesity, and hormone levels in reproductive-aged women","volume":"70","author":"Sierdzinski","year":"2019","journal-title":"Endokrynol. Pol."},{"key":"ref_6","first-page":"219","article-title":"Matrix Metalloproteinase-2 and -9 Levels in Obese Patients","volume":"15","author":"Derosa","year":"2008","journal-title":"Endothel. J. Endothel. Cell Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"287","DOI":"10.2147\/VHRM.S103877","article-title":"Matrix metalloproteinases in exercise and obesity","volume":"12","author":"Jaoude","year":"2016","journal-title":"Vasc. Health Risk Manag."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.matbio.2017.11.007","article-title":"The gelatinases, MMP-2 and MMP-9, as fine tuners of neuroinflammatory processes","volume":"75\u201376","author":"Hannocks","year":"2019","journal-title":"Matrix Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1696","DOI":"10.2741\/1915","article-title":"Matrix metalloproteinases (MMPs) in health and disease: An overview","volume":"11","author":"Malemud","year":"2006","journal-title":"Front. Biosci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1136\/ard.62.suppl_2.ii43","article-title":"Metalloproteinases, inflammation, and rheumatoid arthritis","volume":"62","author":"Mohammed","year":"2003","journal-title":"Ann. Rheum. Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1038\/nri1418","article-title":"Matrix metalloproteinases as modulators of inflammation and innate immunity","volume":"4","author":"Parks","year":"2004","journal-title":"Nat. Rev. Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1111\/eci.12649","article-title":"Association of MMP-8 with obesity, smoking and insulin resistance","volume":"46","author":"Lauhio","year":"2016","journal-title":"Eur. J. Clin. Investig."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1007\/s00109-009-0486-8","article-title":"Increased adipose tissue expression of lipocalin-2 in obesity is related to inflammation and matrix metalloproteinase-2 and metalloproteinase-9 activities in humans","volume":"87","author":"Silva","year":"2009","journal-title":"J. Mol. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2080","DOI":"10.2337\/diabetes.50.9.2080","article-title":"Adipocyte Produces Matrix Metalloproteinases 2 and 9 Involvement in Adipose Differentiation","volume":"50","author":"Portolan","year":"2001","journal-title":"Diabetes"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"11888","DOI":"10.1074\/jbc.M209196200","article-title":"Matrix metalloproteinases are differentially expressed in adipose tissue during obesity and modulate adipocyte differentiation","volume":"278","author":"Chavey","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.1007\/s11033-015-3861-2","article-title":"Inhibition of MMP-13 prevents diet-induced obesity in mice and suppresses adipogenesis in 3T3-L1 preadipocytes","volume":"42","author":"Shih","year":"2015","journal-title":"Mol. Biol. Rep."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1136\/annrheumdis-2011-200123","article-title":"Comparison of rheumatoid articular adipose and synovial tissue reactivity to proinflammatory stimuli: Contribution to adipocytokine network","volume":"71","author":"Kontny","year":"2012","journal-title":"Ann. Rheum. Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1016\/j.joca.2010.03.014","article-title":"The infrapatellar fat pad should be considered as an active osteoarthritic joint tissue: A narrative review","volume":"18","author":"Clockaerts","year":"2010","journal-title":"Osteoarthr. Cartil."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1038\/s41569-018-0097-6","article-title":"The role of adipose tissue in cardiovascular health and disease","volume":"16","author":"Oikonomou","year":"2019","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Garc\u00eda-Alonso, V., Titos, E., Alcaraz-Quiles, J., Rius, B., Lopategi, A., L\u00f3pez-Vicario, C., Jakobsson, P.J., Delgado, S., Lozano, J., and Cl\u00e0ria, J. (2016). Prostaglandin E2 exerts multiple regulatory actions on human obese adipose tissue remodeling, inflammation, adaptive thermogenesis and lipolysis. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0153751"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.mce.2009.07.031","article-title":"Adipokine dysregulation, adipose tissue inflammation and metabolic syndrome","volume":"314","author":"Maury","year":"2010","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1016\/j.beem.2005.07.009","article-title":"Adipose tissue: A regulator of inflammation","volume":"19","author":"Henrichot","year":"2005","journal-title":"Best Pract. Res. Clin. Endocrinol. Metab."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1016\/j.bcp.2019.03.030","article-title":"Adipokines: Linking metabolic syndrome, the immune system, and arthritic diseases","volume":"165","author":"Francisco","year":"2019","journal-title":"Biochem. Pharmacol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1681\/ASN.2015050528","article-title":"PGE2, kidney disease, and cardiovascular risk: Beyond hypertension and diabetes","volume":"27","author":"Nasrallah","year":"2016","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1093\/jmcb\/mjw035","article-title":"Prostaglandin E2 receptor EP3 regulates both adipogenesis and lipolysis in mouse white adipose tissue","volume":"8","author":"Xu","year":"2016","journal-title":"J. Mol. Cell Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"383","DOI":"10.2174\/187153006779025711","article-title":"Role of PGE2 and EP Receptors in the Pathogenesis of Rheumatoid Arthritis and as a Novel Therapeutic Strategy","volume":"6","author":"Akaogi","year":"2012","journal-title":"Endocr. Metab. Immune Disord.-Drug Targets"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1016\/j.berh.2016.02.003","article-title":"Lipid mediators of inflammation in rheumatoid arthritis and osteoarthritis","volume":"29","author":"Brouwers","year":"2015","journal-title":"Best Pract. Res. Clin. Rheumatol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"290","DOI":"10.4161\/adip.29993","article-title":"Prostaglandin E 2 signals white-to-brown adipogenic differentiation","volume":"3","year":"2014","journal-title":"Adipocyte"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1904","DOI":"10.2337\/db12-0769","article-title":"Prostaglandin E2 receptor, EP3, is induced in diabetic islets and negatively regulates glucose- and hormone- stimulated insulin secretion","volume":"62","author":"Kimple","year":"2013","journal-title":"Diabetes"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1006\/bbrc.2000.3168","article-title":"Regulation of leptin release by mammalian adipose tissue","volume":"274","author":"Fain","year":"2000","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_31","first-page":"665","article-title":"Insights into the roles of the inflammatory mediators IL-1, IL-18 and PGE2 in obesity and insulin resistance","volume":"138","author":"Osborn","year":"2008","journal-title":"Swiss Med. Wkly."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Engin, A.B., and Engin, A. (2017). Obesity and Lipotoxicity, Springer.","DOI":"10.1007\/978-3-319-48382-5"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.coph.2017.08.006","article-title":"Adipose tissue inflammation in obesity: A metabolic or immune response?","volume":"37","author":"Stolarczyk","year":"2017","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1038\/nrendo.2009.264","article-title":"Inflammatory lipid mediators in adipocyte function and obesity","volume":"6","author":"Iyer","year":"2010","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Dordevic, A.L., Konstantopoulos, N., and Cameron-Smith, D. (2014). 3T3-L1 preadipocytes exhibit heightened monocyte-chemoattractant protein-1 response to acute fatty acid exposure. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0099382"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"E576","DOI":"10.1152\/ajpendo.00523.2006","article-title":"Palmitate modulates intracellular signaling, induces endoplasmic reticulum stress, and causes apoptosis in mouse 3T3-L1 and rat primary preadipocytes","volume":"293","author":"Guo","year":"2007","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"5340","DOI":"10.1210\/en.2006-0536","article-title":"Preadipocytes mediate lipopolysaccharide-induced inflammation and insulin resistance in primary cultures of newly differentiated human adipocytes","volume":"147","author":"Chung","year":"2006","journal-title":"Endocrinology"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"S17","DOI":"10.1016\/S0049-3848(11)70006-8","article-title":"Murine models of obesity and hormonal therapy","volume":"127","author":"Lijnen","year":"2011","journal-title":"Thromb. Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2954","DOI":"10.1016\/j.bbagen.2012.12.024","article-title":"Macrophage elastase (MMP-12) in expanding murine adipose tissue","volume":"1830","author":"Bauters","year":"2013","journal-title":"Biochim. Biophys. Acta Gen. Subj."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1111\/1440-1681.12154","article-title":"Differential effects of a gelatinase inhibitor on adipocyte differentiation and adipose tissue development","volume":"40","author":"Bauters","year":"2013","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/0014-5793(93)80312-I","article-title":"Astacins, serralysins, snake venom and matrix metalloproteinases exhibit identical zinc-binding environments (HEXXHXXGXXH and Met-turn) and topologies and should be grouped into a common family, the \u201cmetzincins\u201d","volume":"331","author":"Bode","year":"1993","journal-title":"FEBS Lett."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Camacho, E., Sanz, L., Escalante, T., P\u00e9rez, A., Villalta, F., Lomonte, B., Neves-Ferreira, A.G.C., Feoli, A., Calvete, J.J., and Guti\u00e9rrez, J.M. (2016). Novel catalytically-inactive PII metalloproteinases from a viperid snake venom with substitutions in the canonical zinc-binding motif. Toxins, 8.","DOI":"10.3390\/toxins8100292"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Parks, W.C. (2006). Matrix Metalloproteinases. Encycl. Respir. Med. Four Vol. Set, 18\u201325.","DOI":"10.1016\/B0-12-370879-6\/00234-9"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"3016","DOI":"10.1111\/j.1742-4658.2008.06466.x","article-title":"Insights into and speculations about snake venom metalloproteinase (SVMP) synthesis, folding and disulfide bond formation and their contribution to venom complexity","volume":"275","author":"Fox","year":"2008","journal-title":"FEBS J."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1016\/0076-6879(95)48023-4","article-title":"Snake venom metalloendopeptidases: Reprolysins","volume":"248","author":"Bjarnason","year":"1995","journal-title":"Methods Enzymol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.bbapap.2011.04.009","article-title":"Snake venom metalloproteinases: Structure, function and relevance to the mammalian ADAM\/ADAMTS family proteins","volume":"1824","author":"Takeda","year":"2012","journal-title":"Biochim. Biophys. Acta Proteins Proteom."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1016\/j.toxicon.2007.11.017","article-title":"Isolation and structural characterization of a new fibrin(ogen)olytic metalloproteinase from Bothrops moojeni snake venom","volume":"51","author":"Bernardes","year":"2008","journal-title":"Toxicon"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Pidde-Queiroz, G., Magnoli, F.C., Portaro, F.C., Serrano, S.M., Lopes, A.S., Paes Leme, A.F., van den Berg, C.W., and Tambourgi, D.V. (2013). P-I snake venom metalloproteinase is able to activate the complement system by direct cleavage of central components of the cascade. PLoS Negl. Trop. Dis., 7.","DOI":"10.1371\/journal.pntd.0002519"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2241","DOI":"10.1016\/S0021-9258(17)42159-4","article-title":"Monomeric Re lipopolysaccharide from Escherichia coli is more active than the aggregated form in the Limulus amebocyte lysate assay and in inducing Egr-1 mRNA in murine peritoneal macrophages","volume":"269","author":"Takayama","year":"1994","journal-title":"J. Biol. Chem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1189\/jlb.0510263","article-title":"A group IIA-secreted phospholipase A2 from snake venom induces lipid body formation in macrophages: The roles of intracellular phospholipases A2 and distinct signaling pathways","volume":"90","author":"Leiguez","year":"2011","journal-title":"J. Leukoc. Biol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1385\/ABAB:118:1-3:097","article-title":"Control of Life Cycle of Mouse Adipogenic 3T3-L1 Cells","volume":"118","author":"Nishimura","year":"2004","journal-title":"Appl. Biochem. Biotechnol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2145","DOI":"10.1271\/bbb.60106","article-title":"Endogenous prostaglandins E2 and F2\u03b1 serve as an anti-apoptotic factor against apoptosis induced by tumor necrosis factor-\u03b1 in mouse 3T3-L1 preadipocytes","volume":"70","author":"Nishimura","year":"2006","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"33975","DOI":"10.1074\/jbc.M805817200","article-title":"Smooth muscle cell arachidonic acid release, migration, and proliferation are markedly attenuated in mice null for calcium-independent phospholipase A2\u03b2","volume":"283","author":"Sung","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-017-04498-8","article-title":"A snake venom group IIA PLA2 with immunomodulatory activity induces formation of lipid droplets containing 15-d-PGJ2 in macrophages","volume":"7","author":"Giannotti","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2320","DOI":"10.2337\/db11-1179","article-title":"An inhibitor of phospholipase A 2 group IIA modulates adipocyte signaling and protects against diet-induced metabolic syndrome in rats","volume":"61","author":"Iyer","year":"2012","journal-title":"Diabetes"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2421","DOI":"10.1038\/jid.2008.118","article-title":"Skin pathology induced by snake venom metalloproteinase: Acute damage, revascularization, and re-epithelization in a mouse ear model","volume":"128","author":"Escalante","year":"2008","journal-title":"J. Investig. Dermatol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1128\/microbiolspec.MCHD-0035-2016","article-title":"Lipid Mediators in Inflammation","volume":"4","author":"Bennett","year":"2016","journal-title":"Microbiol. Spectr."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1084\/jem.20051310","article-title":"Prostacyclin-IP signaling and prostaglandin E2-EP2\/EP4 signaling both mediate joint inflammation in mouse collagen-induced arthritis","volume":"203","author":"Honda","year":"2006","journal-title":"J. Exp. Med."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1093\/intimm\/dxz021","article-title":"Molecular mechanisms underlying prostaglandin E2-exacerbated inflammation and immune diseases","volume":"31","author":"Tsuge","year":"2019","journal-title":"Int. Immunol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1194\/jlr.R800094-JLR200","article-title":"Prostanoids in health and disease","volume":"50","author":"Smyth","year":"2009","journal-title":"J. Lipid Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"8119","DOI":"10.4049\/jimmunol.0901925","article-title":"Matrix Metalloproteinase (MMP)-1 and MMP-3 Induce Macrophage MMP-9: Evidence for the Role of TNF-\u03b1 and Cyclooxygenase-2","volume":"183","author":"Steenport","year":"2009","journal-title":"J. Immunol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/j.clim.2006.01.016","article-title":"Prostaglandin E2 synthesis and secretion: The role of PGE2 synthases","volume":"119","author":"Park","year":"2006","journal-title":"Clin. Immunol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1038","DOI":"10.1111\/bph.14167","article-title":"Eicosanoids, prostacyclin and cyclooxygenase in the cardiovascular system","volume":"176","author":"Mitchell","year":"2019","journal-title":"Br. J. Pharmacol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"313","DOI":"10.4269\/ajtmh.2000.63.313","article-title":"Inhibition of local hemorrhage and dermonecrosis induced by Bothrops asper snake venom: Effectiveness of early in situ administration of the peptidomimetic metalloproteinase inhibitor batimastat and the chelating agent CaNa2EDTA","volume":"63","author":"Rucavado","year":"2000","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Li, A., Yu, H., Li, R., Liu, S., Xing, R., and Li, P. (2019). Inhibitory effect of metalloproteinase inhibitors on skin cell inflammation induced by jellyfish nemopilema nomurai nematocyst venom. Toxins, 11.","DOI":"10.3390\/toxins11030156"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S1388-1981(00)00105-0","article-title":"The expanding superfamily of phospholipase A2 enzymes: Classification and characterization","volume":"1488","author":"Six","year":"2000","journal-title":"Biochim. Biophys. Acta Mol. Cell Biol. Lipids"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.cytogfr.2018.10.002","article-title":"Pro-inflammatory cytokines: The link between obesity and osteoarthritis","volume":"44","author":"Wang","year":"2018","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1016\/j.jaci.2005.02.023","article-title":"Adipose tissue, adipokines, and inflammation","volume":"115","author":"Fantuzzi","year":"2005","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1038\/nri1937","article-title":"Adipocytokines: Mediators linking adipose tissue, inflammation and immunity","volume":"6","author":"Tilg","year":"2006","journal-title":"Nat. Rev. Immunol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1016\/j.tips.2015.04.014","article-title":"Adipokines in health and disease","volume":"36","author":"Fasshauer","year":"2015","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2010\/802078","article-title":"The role of adipose tissue and adipokines in obesity-related inflammatory diseases","volume":"2010","author":"Balistreri","year":"2010","journal-title":"Mediat. Inflamm."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-020-59095-z","article-title":"A representative metalloprotease induces PGE2 synthesis in fibroblast-like synoviocytes via the NF-\u03baB\/COX-2 pathway with amplification by IL-1\u03b2 and the EP4 receptor","volume":"10","author":"Viana","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1007\/s00109-009-0500-1","article-title":"Prostanoids and inflammation: A new concept arising from receptor knockout mice","volume":"87","author":"Narumiya","year":"2009","journal-title":"J. Mol. Med."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.prostaglandins.2011.06.002","article-title":"15-Deoxy-\u0394 12,14-prostaglandin J 2 interferes inducible synthesis of prostaglandins E 2 and F 2\u03b1 that suppress subsequent adipogenesis program in cultured preadipocytes","volume":"95","author":"Chowdhury","year":"2011","journal-title":"Prostaglandins Lipid Mediat."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"3254","DOI":"10.1002\/jcp.26932","article-title":"Prostacyclin: A major prostaglandin in the regulation of adipose tissue development","volume":"234","author":"Rahman","year":"2019","journal-title":"J. Cell. Physiol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1038\/nrrheum.2011.107","article-title":"What\u2019s new in our understanding of the role of adipokines in rheumatic diseases?","volume":"7","author":"Conde","year":"2011","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1136\/gut.2004.059824","article-title":"Monocyte chemoattractant protein 1 and macrophage cyclooxygenase 2 expression in colonic adenoma","volume":"55","author":"Tanaka","year":"2006","journal-title":"Gut"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1257","DOI":"10.1136\/gut.52.9.1257","article-title":"Monocyte chemoattractant protein 1 (MCP-1) released from Helicobacter pylori stimulated gastric epithelial cells induces cyclooxygenase 2 expression and activation in T cells","volume":"52","author":"Futagami","year":"2003","journal-title":"Gut"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/S0065-2776(01)77017-4","article-title":"Diversity and regulatory functions of mammalian secretory phospholipase A2s","volume":"77","author":"Murakami","year":"2001","journal-title":"Adv. Immunol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1210\/jc.2009-1222","article-title":"Secretory type II phospholipase A2 is produced and secreted by epicardial adipose tissue and overexpressed in patients with coronary artery disease","volume":"95","author":"Dutour","year":"2010","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1093\/jb\/mvr088","article-title":"Secreted phospholipase A 2 revisited","volume":"150","author":"Murakami","year":"2011","journal-title":"J. Biochem."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1246","DOI":"10.1016\/j.bbalip.2006.07.011","article-title":"The phospholipase A2 superfamily and its group numbering system","volume":"1761","author":"Schaloske","year":"2006","journal-title":"Biochim. Biophys. Acta Mol. Cell Biol. Lipids"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"2023","DOI":"10.1038\/oby.2010.9","article-title":"High plasma phospholipase A 2 activity, inflammation markers, and LDL alterations in obesity with or without type 2 diabetes","volume":"18","author":"Garces","year":"2010","journal-title":"Obesity"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"e002553","DOI":"10.1161\/JAHA.115.001868","article-title":"Yun, T.; Lee, J.S.; Filep, J.G.; Kassiri, Z.; Cheong, C.; Lambeau, G.; et al. Identification of a Novel Heart-Liver Axis: Matrix Metalloproteinase-2 Negatively Regulates Cardiac Secreted Phospholipase A2 to Modulate Lipid Metabolism and Inflammation in the Liver","volume":"4","author":"Berry","year":"2015","journal-title":"J. Am. Heart Assoc."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"e001868","DOI":"10.1161\/JAHA.115.001868","article-title":"Matrix metalloproteinase-2 negatively regulates cardiac secreted phospholipase A2 to modulate inflammation and fever","volume":"4","author":"Berry","year":"2015","journal-title":"J. Am. Heart Assoc."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"607186","DOI":"10.3389\/fmed.2020.607186","article-title":"The Damage-Associated Molecular Patterns (DAMPs) as Potential Targets to Treat Osteoarthritis: Perspectives From a Review of the Literature","volume":"7","author":"Lambert","year":"2021","journal-title":"Front. Med."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"38969","DOI":"10.1074\/jbc.M509352200","article-title":"Toll-like receptor 4 signaling regulates cytosolic phospholipase A2 activation and lipid generation in lipopolysaccharide-stimulated macrophages","volume":"280","author":"Qi","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Guti\u00e9rrez, J.M., Escalante, T., Rucavado, A., Herrera, C., and Fox, J.W. (2016). A Comprehensive View of the Structural and Functional Alterations of Extracellular Matrix by Snake Venom Metalloproteinases (SVMPs): Novel Perspectives on the Pathophysiology of Envenoming. Toxins, 8.","DOI":"10.3390\/toxins8100304"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1161\/ATVBAHA.110.219527","article-title":"Protease-activated receptor signaling in platelets activates cytosolic phospholipase A2\u03b1 differently for cyclooxygenase-1 and 12-lipoxygenase catalysis","volume":"31","author":"Holinstat","year":"2011","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_90","first-page":"1","article-title":"Contribution of adipose tissue inflammation to the development of type 2 diabetes HHS Public Access","volume":"9","author":"Burhans","year":"2019","journal-title":"Physiol. Behav."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1007\/s10753-018-0901-9","article-title":"Different Secretory Activity of Articular and Subcutaneous Adipose Tissues from Rheumatoid Arthritis and Osteoarthritis Patients","volume":"42","author":"Radzikowska","year":"2019","journal-title":"Inflammation"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"6010","DOI":"10.1074\/jbc.271.11.6010","article-title":"Inhibition of monocyte chemotaxis to C-C chemokines by antisense oligonucleotide for cytosolic phospholipase A2","volume":"271","author":"Locati","year":"1996","journal-title":"J. Biol. Chem."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.1016\/j.bone.2009.02.015","article-title":"Proteinase-activated receptor (PAR)-2 activation impacts bone resorptive properties of human osteoarthritic subchondral bone osteoblasts","volume":"44","author":"Amiable","year":"2009","journal-title":"Bone"}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/11\/7\/921\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:20:58Z","timestamp":1760163658000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/11\/7\/921"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,22]]},"references-count":93,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2021,7]]}},"alternative-id":["biom11070921"],"URL":"https:\/\/doi.org\/10.3390\/biom11070921","relation":{},"ISSN":["2218-273X"],"issn-type":[{"type":"electronic","value":"2218-273X"}],"subject":[],"published":{"date-parts":[[2021,6,22]]}}}