{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T08:54:00Z","timestamp":1789894440846,"version":"4.0.1"},"reference-count":50,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2013,3,28]],"date-time":"2013-03-28T00:00:00Z","timestamp":1364428800000},"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":[[2013,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>To evaluate the requirement for protein kinase C\u03b2 (PKC\u03b2) in the development of lupus in mice, and to explore the potential of targeting PKC\u03b2 as a therapeutic strategy in lupus.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Congenic mice bearing the disease loci <jats:italic>Sle1<\/jats:italic> or <jats:italic>Sle1<\/jats:italic> and <jats:italic>Sle3<\/jats:italic>, which represent different stages of severity in the development of lupus, were crossed with PKC\u03b2\u2010deficient mice. The effect of PKC\u03b2 deficiency in lupus development was analyzed. In addition, the effects of the PKC\u03b2\u2010specific inhibitor enzastaurin on the survival of B cells from mice with lupus and human 9G4\u2010positive B cells as well as the in vivo effect of enzastaurin treatment on the development of lupus in Sle mice were investigated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In Sle mice, PKC\u03b2 deficiency abrogated lupus\u2010associated phenotypes, including high autoantibody levels, proteinuria, and histologic features of lupus nephritis. Significant decreases in spleen size and in the peritoneal B\u20101 cell population, reduced numbers of activated CD4 T cells, and normalized CD4:CD8 ratios were observed. PKC\u03b2 deficiency induced an anergic B cell phenotype and preferentially inhibited autoreactive plasma cells and autoantibodies in mice with lupus. Inhibition of PKC\u03b2 enhanced apoptosis of both B cells from Sle mice and human autoreactive B cells (9G4 positive). Treatment of Sle mice with the PKC\u03b2\u2010specific inhibitor enzastaurin prevented the development of lupus.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study identifies PKC\u03b2 as a central mediator of lupus pathogenesis, suggesting that PKC\u03b2 represents a promising therapeutic target for the treatment of systemic lupus erythematosus. Moreover, the results indicate the feasibility of using a PKC\u03b2 inhibitor for the treatment of lupus.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.37825","type":"journal-article","created":{"date-parts":[[2012,12,22]],"date-time":"2012-12-22T06:15:29Z","timestamp":1356156929000},"page":"1022-1031","source":"Crossref","is-referenced-by-count":16,"title":["Protein Kinase C\u03b2 Is Required for Lupus Development in Sle 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