{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T08:38:49Z","timestamp":1793176729436,"version":"4.5.0"},"reference-count":33,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2015,11,4]],"date-time":"2015-11-04T00:00:00Z","timestamp":1446595200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[2016,1]]},"abstract":"<jats:p>Gout manifests as recurrent episodes of acute joint inflammation and pain due to the deposition of monosodium urate (MSU) crystals within the affected tissue in a process dependent on NLRP3 inflammasome activation. The synthesis, activation, and release of IL\u20101\u03b2 are crucial for MSU\u2010induced inflammation. The current study evaluated the mechanism by which TNF\u2010\u03b1 contributed to MSU\u2010induced inflammation. Male C57BL\/6J or transgenic mice were used in this study and inflammation was induced by the injection of MSU crystals into the joint. TNF\u2010\u03b1 was markedly increased in the joint after the injection of MSU. There was inhibition in the infiltration of neutrophils, production of CXCL1 and IL\u20101\u03b2, and decreased hypernociception in mice deficient for TNF\u2010\u03b1 or its receptors. Pharmacological blockade of TNF\u2010\u03b1 with Etanercept or pentoxyfylline produced similar results. Mechanistically, TNF\u2010\u03b1 blockade resulted in lower amounts of IL\u20101\u03b2 protein and pro\u2010IL\u20101\u03b2 mRNA transcripts in joints. Gene\u2010modified mice that express only transmembrane TNF\u2010\u03b1 had an inflammatory response similar to that of WT mice and blockade of soluble TNF\u2010\u03b1 (XPro\u21221595) did not decrease MSU\u2010induced inflammation. In conclusion, TNF\u2010\u03b1 drives expression of pro\u2010IL\u20101\u03b2 mRNA and IL\u20101\u03b2 protein in experimental gout and that its transmembrane form is sufficient to trigger MSU\u2010induced inflammation in mice.<\/jats:p>","DOI":"10.1002\/eji.201545798","type":"journal-article","created":{"date-parts":[[2015,10,9]],"date-time":"2015-10-09T09:10:38Z","timestamp":1444381838000},"page":"204-211","source":"Crossref","is-referenced-by-count":79,"title":["Transmembrane TNF\u2010\u03b1 is sufficient for articular inflammation and hypernociception in a mouse model of gout"],"prefix":"10.1002","volume":"46","author":[{"given":"Fl\u00e1vio A.","family":"Amaral","sequence":"first","affiliation":[{"name":"Immunopharmacology Lab Department of Biochemistry and Immunology Federal University of Minas  Gerais Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leandro F. 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