{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T10:13:08Z","timestamp":1790935988997,"version":"4.1.0"},"reference-count":51,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2004,8,5]],"date-time":"2004-08-05T00:00:00Z","timestamp":1091664000000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2004,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>NF\u2010\u03baB activation is associated with several inflammatory disorders, including rheumatoid arthritis (RA), making this family of transcription factors a good target for the development of antiinflammatory treatments. Although inhibitors of the NF\u2010\u03baB pathway are currently available, their specificity has not been adequately determined. I\u03baB\u03b1 is a physiologic inhibitor of NF\u2010\u03baB and a potent repressor experimentally when expressed in a nondegradable form. We describe here a novel means for specifically regulating NF\u2010\u03baB activity in vivo by administering a chimeric molecule comprising the super\u2010repressor I\u03baB\u03b1 (srI\u03baB\u03b1) fused to the membrane\u2010transducing domain of the human immunodeficiency virus Tat protein (Tat\u2010srI\u03baB\u03b1).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The Wistar rat carrageenan\u2010induced pleurisy model was used to assess the effects of in vivo administration of Tat\u2010srI\u03baB\u03b1 on leukocyte infiltration and on cytokine and chemokine production.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Systemic administration of Tat\u2010srI\u03baB\u03b1 diminished infiltration of leukocytes into the site of inflammation. Analysis of the recruited inflammatory cells confirmed uptake of the inhibitor and reduction of the NF\u2010\u03baB activity. These cells exhibited elevated caspase activity, suggesting that NF\u2010\u03baB is required for the survival of leukocytes at sites of inflammation. Analysis of exudates, while showing decreases in the production of the proinflammatory cytokines tumor necrosis factor \u03b1 and interleukin\u20101\u03b2, also revealed a significant increase in the production of the neutrophil chemoattractants cytokine\u2010induced neutrophil chemoattractant 1 (CINC\u20101) and CINC\u20103 compared with controls. This result could reveal a previously unknown feedback mechanism in which infiltrating leukocytes may down\u2010regulate local production of these chemokines.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These results provide new insights into the etiology of inflammation and establish a strategy for developing novel therapeutics by regulating the signaling activity of pathways known to function in RA.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.20467","type":"journal-article","created":{"date-parts":[[2004,8,9]],"date-time":"2004-08-09T18:19:36Z","timestamp":1092075576000},"page":"2675-2684","source":"Crossref","is-referenced-by-count":36,"title":["Reduced infiltration and increased apoptosis of leukocytes at sites of inflammation by systemic administration of a membrane\u2010permeable I\u03baB\u03b1 repressor"],"prefix":"10.1002","volume":"50","author":[{"given":"Nathan 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