{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T00:08:48Z","timestamp":1793664528970,"version":"4.5.1"},"reference-count":60,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,1,9]],"date-time":"2023-01-09T00:00:00Z","timestamp":1673222400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006668","name":"Fondo para la Investigaci\u00f3n Cient\u00edfica y Tecnol\u00f3gica","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006668","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Spondyloarthritis (SpA) is a common autoinflammatory disease. S100A8\/ S100A9 alarmin is strongly expressed in the synovial sublining layers of psoriatic arthritis. S100A8\/ S100A9 is the most abundant protein in rheumatoid arthritis synovial fluid (SF) and has a key role in promoting IL-6 expression in fibroblast-like synoviocytes (FLS). The molecular mechanisms and the role of S100-alarmins in the synovial microenvironment of SpA have never been demonstrated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and Results<\/jats:title>\n                    <jats:p>Here, we confirm the effect of the synovial microenvironment of peripheral SpA on interleukin-6 (IL-6) and metalloproteinase (MMP)-9 production by FLS. MMP-9 expression and activity were detected, which were reduced in the presence of anti-IL-6R. Analyzing cell signaling mechanisms, we found that stimulation with IL-6 co-triggered MMP-9 and IL-10 secretion. MMP-9 secretion depended on JNK and p38 MAPKs, whereas IL-10 secretion was dependent on the JAK pathway as a potential feedback mechanism controlling IL-6-induced MMP-9 expression. Using a proteomic approach, we identified S100A8 in the peripheral SpA SF. This presence was confirmed by immunoblotting. S100A8 increased the IL-6 secretion via ERK and p38 MAPK pathways. Furthermore, anti-S100A8\/A9 reduced both IL-6 and MMP-9 production induced by SpA SF in FLS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Our data reveal a marked relationship between S100A8 alarmin with IL-6 and MMP-9 secretion by FLS in the real synovial microenvironment of peripheral SpA. These results identify a mechanism linking S100A8 to the pathogenesis of peripheral SpA.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2022.1077914","type":"journal-article","created":{"date-parts":[[2023,1,10]],"date-time":"2023-01-10T07:47:55Z","timestamp":1673336875000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":11,"title":["S100A8 alarmin supports IL-6 and metalloproteinase-9 production by fibroblasts in the synovial microenvironment of peripheral spondyloarthritis"],"prefix":"10.3389","volume":"13","author":[{"given":"Jos\u00e9 L.","family":"Arias","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samanta 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