{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T03:41:38Z","timestamp":1792899698595,"version":"4.5.0"},"reference-count":64,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2022,5,7]],"date-time":"2022-05-07T00:00:00Z","timestamp":1651881600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Heart, Lung, and Blood Institute, National Institutes of Health, USA","award":["R01 HL116042"],"award-info":[{"award-number":["R01 HL116042"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJERPH"],"abstract":"<jats:p>Osteoarthritis (OA) is a chronic inflammatory disease where pro-inflammatory cytokines, damage-associated molecular patterns (DAMPs), and macrophages play a crucial role. However, the interactive role of these mediators, the exact cause precipitating OA and definitive treatment for OA are not known yet. Moreover, the interactive role of interleukin (IL)-33 and IL-37 with other factors in the pathogenesis of OA has not been discussed elaborately. In this study, we analyzed the expression of IL-33 and IL-37 in human OA knee and hip joint cartilage tissues. The effect of increased DAMPs, IL-33, and IL-37 on IL-6, tumor necrosis factor (TNF)-\u03b1, toll-like receptors (TLRs), and matrix metalloproteinases (MMPs) expression was delineated using human normal and osteoarthritic chondrocytes. The effect of anti-inflammatory cytokine IL-37 on various mediators of inflammation in the presence of IL-33, rHMGB-1, and LPS was investigated to delineate the effects of IL-37. Further, the effects of blocking IL-33 downstream signaling and the effects of IL-33 and IL-37 on macrophage polarization were assessed along with examining the macrophage phenotypes in human OA cartilage tissues. The results of this study revealed increased expression of IL-33 in OA cartilage and that IL-33 increases IL-6, TNF-\u03b1, TLRs, and MMPs expression and favors phenotypic conversion towards the M1 phenotype, while IL-37 and blocking IL-33 receptor ST2 have opposite effects. Overall, the results suggest that blocking IL-33 and increasing IL-37 act synergistically to attenuate inflammation and might serve as potential therapeutics in OA.<\/jats:p>","DOI":"10.3390\/ijerph19095690","type":"journal-article","created":{"date-parts":[[2022,5,8]],"date-time":"2022-05-08T08:04:21Z","timestamp":1651997061000},"page":"5690","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Counteractive Effects of IL-33 and IL-37 on Inflammation in Osteoarthritis"],"prefix":"10.3390","volume":"19","author":[{"given":"Vikrant","family":"Rai","sequence":"first","affiliation":[{"name":"Department of Translational Research, Western University of Health Sciences, Pomona, CA 91766, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew F.","family":"Dilisio","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Creighton University School of Medicine, Omaha, NE 68178, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farial","family":"Samadi","sequence":"additional","affiliation":[{"name":"Department of Biology, College of Arts and Sciences, University of Nebraska at Omaha, Omaha, NE 68182, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5445-0013","authenticated-orcid":false,"given":"Devendra K.","family":"Agrawal","sequence":"additional","affiliation":[{"name":"Department of Translational Research, Western University of Health Sciences, Pomona, CA 91766, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,7]]},"reference":[{"key":"ref_1","first-page":"327","article-title":"Efficacy and safety of hylan G-F 20 injection in treatment of knee osteoarthritis in Chinese patients: Results of a prospective, multicentre, longitudinal study","volume":"21","author":"Yan","year":"2015","journal-title":"Hong Kong Med. 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