{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T12:37:19Z","timestamp":1773146239716,"version":"3.50.1"},"reference-count":33,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2012,1,27]],"date-time":"2012-01-27T00:00:00Z","timestamp":1327622400000},"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":[[2012,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Both type I interferons (IFN\u03b1 and IFN\u03b2) and type II IFN (IFN\u03b3) signal via pSTAT\u20101. Immunohistochemistry and the gene expression signatures of rheumatoid arthritis (RA) synovial tissue suggest an activated IFN\/STAT\u20101 signaling pathway. The aim of this study was to determine the systemic activity of the IFN\/STAT\u20101 signaling pathway in the peripheral blood cells of patients with RA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Fluorocytometry or quantitative polymerase chain reaction was used to measure the expression of STAT\u20101, pSTAT\u20101, and IFN\u2010inducible genes (monokine induced by interferon\u2010\u03b3 [MIG], interferon\u2010\u03b3\u2013inducible protein 10 [IP\u201010], and 2\u2032,5\u2032\u2010oligoadenylate synthetase [OAS]) in the peripheral blood mononuclear cells (PBMCs) and purified CD14+ peripheral blood monocytes of patients with RA and healthy control subjects. PBMCs were also incubated for 48 hours with IFNs and several other cytokines to investigate influences on STAT\u20101 levels. To examine the significance of STAT\u20101 activation in RA monocytes after stimulation with IFN\u03b3, the expression of pSTAT\u20101 and of the IFN\u03b3\u2010inducible chemokine MIG was measured using fluorocytometry.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Levels of STAT\u20101 were significantly increased in peripheral lymphocytes and monocytes from patients with RA compared with those from healthy control subjects. STAT\u20101 levels correlated well with RA disease activity, as measured by the Disease Activity Score in 28 joints and the Clinical Disease Activity Index. Furthermore, STAT\u20101 messenger RNA expression in RA CD14+ monocytes correlated with the expression of other IFN\u2010target genes, such as IP\u201010, OAS, or MIG. In RA PBMCs, STAT\u20101 expression was increased not only by IFNs but also by tumor necrosis factor. RA monocytes demonstrated a considerably higher increase in pSTAT\u20101 and MIG levels upon IFN\u03b3 stimulation when compared with monocytes from control subjects, indicating that RA monocytes are more sensitive to IFN\u03b3 stimulation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In addition to supporting the role of IFNs in systemic proinflammatory activity, the results of this study further suggest preactivation of the IFN\u03b3\/STAT\u20101 signaling pathway, especially in RA monocytes.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.33347","type":"journal-article","created":{"date-parts":[[2011,9,28]],"date-time":"2011-09-28T02:34:46Z","timestamp":1317177286000},"page":"400-408","source":"Crossref","is-referenced-by-count":31,"title":["Interferon signals and monocytic sensitization of the interferon\u2010\u03b3 signaling pathway in the peripheral blood of patients with rheumatoid arthritis"],"prefix":"10.1002","volume":"64","author":[{"given":"Thomas","family":"Karonitsch","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karolina","family":"von Dalwigk","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carl W.","family":"Steiner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephan","family":"Bl\u00fcml","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G\u00fcnter","family":"Steiner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hans P.","family":"Kiener","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Josef 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