{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T01:51:24Z","timestamp":1787968284301,"version":"build-2784847793"},"reference-count":39,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2021,9,21]],"date-time":"2021-09-21T00:00:00Z","timestamp":1632182400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The inflammatory cytokine interleukin-26 (IL-26) is highly expressed in the serum and synovial fluid of patients with inflammatory arthritis. The effect of IL-26 on human articular chondrocytes (HACs) remains unclear. Obesity is associated with disability of patients with rheumatoid arthritis and disease activity in those with ankylosing spondylitis. The saturated free fatty acid palmitate with IL-1\u03b2 can synergistically induce catabolic effects in HACs. The aim of this study was to evaluate the effects of IL-26 and palmitate in HACs. In this study, palmitate markedly synergizes the IL-26-induced proinflammatory effects and matrix protease, including COX-2, IL-6, and MMP-1, in HACs via the toll-like receptor 4 (TLR4)-ERK1\/2-c-Jun signal transduction pathway. The synergistic catabolic effects of palmitate and IL-26 were attenuated by inhibitors of TLR4 (TAK242), ERK1\/2 (U0126), or c-Jun (SP600125) in HACs and cartilage matrix. In addition, metformin, a potential inhibitor of TLR4, also decreased expression of COX-2 and IL-6 induced by co-incubation with IL-26 and palmitate. IL-26 and palmitate synergistically induced expression of inflammatory and catabolic mediators, resulting in articular cartilage matrix breakdown. The present study also revealed a possible mechanism and therapeutic targets against articular cartilage degradation by increased saturated fatty acids in patients with inflammatory arthritis.<\/jats:p>","DOI":"10.3390\/cells10092500","type":"journal-article","created":{"date-parts":[[2021,9,21]],"date-time":"2021-09-21T08:04:23Z","timestamp":1632211463000},"page":"2500","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Interleukin-26 Has Synergistic Catabolic Effects with Palmitate in Human Articular Chondrocytes via the TLR4-ERK1\/2-c-Jun Signaling Pathway"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6108-8646","authenticated-orcid":false,"given":"Yi-Ting","family":"Chen","sequence":"first","affiliation":[{"name":"Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei 114, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chih-Chien","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chia-Pi","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department and Graduate Institute of Biology and Anatomy, National Defense Medical Center, Taipei 114, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng-Cheng","family":"Liu","sequence":"additional","affiliation":[{"name":"Rheumatology\/Immunology and Allergy, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chian-Her","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, School of Medicine, College of Medicine, Taipei Medical University and Hospital, Taipei 114, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Herng-Sheng","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Kaohsiung Veterans General Hospital, Kaohsiung 813414, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4630-2103","authenticated-orcid":false,"given":"Yi-Jen","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3881","DOI":"10.1128\/JVI.74.8.3881-3887.2000","article-title":"Induction of a novel cellular homolog of interleukin-10, ak155, by transformation of t lymphocytes with herpesvirus saimiri","volume":"74","author":"Knappe","year":"2000","journal-title":"J. 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