{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T14:15:46Z","timestamp":1792678546301,"version":"4.5.0"},"reference-count":49,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2012,11,28]],"date-time":"2012-11-28T00:00:00Z","timestamp":1354060800000},"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":[[2012,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>JAK inhibitors have been developed as antiinflammatory and immunosuppressive agents and are currently undergoing testing in clinical trials. The JAK inhibitors CP\u2010690,550 (tofacitinib) and INCB018424 (ruxolitinib) have demonstrated clinical efficacy in rheumatoid arthritis (RA). However, the mechanisms that mediate the beneficial actions of these compounds are not known. The purpose of this study was to examine the effects of both JAK inhibitors on inflammatory and tumor necrosis factor (TNF) responses in human macrophages.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In vitro studies were performed using peripheral blood macrophages derived from healthy donors and treated with TNF and using synovial fluid macrophages derived from patients with RA. Levels of activated STAT proteins and other transcription factors were detected by Western blotting, and gene expression was measured by real\u2010time polymerase chain reaction analysis. The in vivo effects of JAK inhibitors were evaluated in the K\/BxN serum\u2013transfer model of arthritis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>JAK inhibitors suppressed the activation and expression of STAT\u20101 and downstream inflammatory target genes in TNF\u2010stimulated and RA synovial macrophages. In addition, JAK inhibitors decreased nuclear localization of NF\u2010\u03baB subunits in TNF\u2010stimulated and RA synovial macrophages. CP\u2010690,550 significantly decreased the expression of interleukin\u20106 in synovial macrophages. JAK inhibitors augmented nuclear levels of NF\u2010ATc1 and cJun, followed by increased formation of osteoclast\u2010like cells. CP\u2010690,550 strongly suppressed K\/BxN serum\u2013transfer arthritis, which is dependent on macrophages, but not lymphocytes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our findings demonstrate that JAK inhibitors suppress macrophage activation and attenuate TNF responses and further suggest that suppression of cytokine\/chemokine production and innate immunity contribute to the therapeutic efficacy of JAK inhibitors.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/art.37691","type":"journal-article","created":{"date-parts":[[2012,9,1]],"date-time":"2012-09-01T15:28:24Z","timestamp":1346513304000},"page":"3856-3866","source":"Crossref","is-referenced-by-count":110,"title":["Regulation of inflammatory responses in tumor necrosis factor\u2013activated and rheumatoid arthritis synovial macrophages by JAK inhibitors"],"prefix":"10.1002","volume":"64","author":[{"given":"Anna","family":"Yarilina","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunhin","family":"Chan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lionel B.","family":"Ivashkiv","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,11,28]]},"reference":[{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1004965"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri802"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.med.51.1.207"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2008.00644.x"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2010.10.004"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrd3264"},{"key":"e_1_2_7_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1713"},{"key":"e_1_2_7_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2008.00754.x"},{"key":"e_1_2_7_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm909"},{"key":"e_1_2_7_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/377065a0"},{"key":"e_1_2_7_12_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.16.1.293"},{"key":"e_1_2_7_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81167-8"},{"key":"e_1_2_7_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81166-6"},{"key":"e_1_2_7_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)00055-8"},{"key":"e_1_2_7_16_2","doi-asserted-by":"publisher","DOI":"10.2165\/11588080-000000000-00000"},{"key":"e_1_2_7_17_2","doi-asserted-by":"publisher","DOI":"10.1186\/1476-9255-7-41"},{"key":"e_1_2_7_18_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1003668"},{"key":"e_1_2_7_19_2","doi-asserted-by":"publisher","DOI":"10.2177\/jsci.32.85"},{"key":"e_1_2_7_20_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1600-6143.2003.00281.x"},{"key":"e_1_2_7_21_2","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0504282"},{"key":"e_1_2_7_22_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.tp.0000177643.05739.cd"},{"key":"e_1_2_7_23_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.24505"},{"key":"e_1_2_7_24_2","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0603252"},{"key":"e_1_2_7_25_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.22055"},{"key":"e_1_2_7_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni1576"},{"key":"e_1_2_7_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellimm.2005.04.018"},{"key":"e_1_2_7_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2009.09.002"},{"key":"e_1_2_7_29_2","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2011.150284"},{"key":"e_1_2_7_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80045-X"},{"key":"e_1_2_7_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni828"},{"key":"e_1_2_7_32_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.11096"},{"key":"e_1_2_7_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2006.08.014"},{"key":"e_1_2_7_34_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt1358"},{"key":"e_1_2_7_35_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm801142b"},{"key":"e_1_2_7_36_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1010030108"},{"key":"e_1_2_7_37_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1102703"},{"key":"e_1_2_7_38_2","doi-asserted-by":"publisher","DOI":"10.1038\/416744a"},{"key":"e_1_2_7_39_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.0105-2896.2005.00337.x"},{"key":"e_1_2_7_40_2","doi-asserted-by":"publisher","DOI":"10.1186\/ar3150"},{"key":"e_1_2_7_41_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20020439"},{"key":"e_1_2_7_42_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200526167"},{"key":"e_1_2_7_43_2","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2005.050385"},{"key":"e_1_2_7_44_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.34544"},{"key":"e_1_2_7_45_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2008.00707.x"},{"key":"e_1_2_7_46_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.178.4.2204"},{"key":"e_1_2_7_47_2","doi-asserted-by":"publisher","DOI":"10.1186\/ar1165"},{"key":"e_1_2_7_48_2","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2008.095356"},{"key":"e_1_2_7_49_2","doi-asserted-by":"publisher","DOI":"10.1006\/clim.2000.4957"},{"key":"e_1_2_7_50_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1119303"}],"container-title":["Arthritis 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