{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T07:04:26Z","timestamp":1791875066461,"version":"4.3.4"},"reference-count":49,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2012,9,28]],"date-time":"2012-09-28T00:00:00Z","timestamp":1348790400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2012,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Type I interferons (IFNs) have emerged as potential activators of the IFN signature and elevated STAT\u20101 expression in rheumatoid arthritis (RA) synovium, but mechanisms that induce synovial IFN expression are unknown. Recently, tumor necrosis factor \u03b1 (TNF\u03b1) was shown to induce a delayed IFN response in macrophages. We undertook this study to test whether TNF\u03b1, classically thought to activate inflammatory NF\u2010\u03baB target genes in RA, also contributes to the \u201cIFN signature\u201d in RA synovial macrophages.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Synovial fluid (SF) macrophages purified from 24 patients with RA and 18 patients with spondylarthritides (SpA) were lysed immediately after isolation or were cultured ex vivo in the absence or presence of blockade of endogenous type I IFN or TNF\u03b1. Expression of IFN\u2010inducible target genes was measured by quantitative reverse transcription\u2013polymerase chain reaction, and expression of their corresponding proteins was measured by enzyme\u2010linked immunosorbent assay.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Expression of an IFN signature and <jats:italic>STAT1<\/jats:italic> in RA synovial macrophages was suppressed when type I IFNs or TNF\u03b1 were blocked, whereas TNF\u03b1 blockade did not affect expression of IFN response genes or <jats:italic>STAT1<\/jats:italic> in SpA synovial macrophages. RA SF suppressed the IFN signature in RA synovial macrophages and in TNF\u03b1\u2010, IFN\u03b1\u2010, and IFN\u03b2\u2010stimulated control macrophages. Type I IFNs suppressed expression of <jats:italic>IL8<\/jats:italic> and <jats:italic>MMP9<\/jats:italic> in RA synovial macrophages and in TNF\u03b1\u2010stimulated control macrophages.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our findings identify a new function of TNF\u03b1 in RA synovitis by implicating TNF\u03b1 as a major inducer of the RA synovial IFN response. The results suggest that the expression of IFN response genes in RA synovium is regulated by interplay between TNF\u03b1 and opposing homeostatic factors expressed in the synovial microenvironment.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.34544","type":"journal-article","created":{"date-parts":[[2012,5,21]],"date-time":"2012-05-21T16:06:20Z","timestamp":1337616380000},"page":"3119-3128","source":"Crossref","is-referenced-by-count":55,"title":["The interferon signature and <i>STAT1<\/i> expression in rheumatoid arthritis synovial fluid macrophages are induced by tumor necrosis factor \u03b1 and counter\u2010regulated by the synovial fluid microenvironment"],"prefix":"10.1002","volume":"64","author":[{"given":"Rachael 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