Your browser doesn't support javascript.
loading
Protein kinase Cß is required for lupus development in Sle mice.
Oleksyn, David; Pulvino, Mary; Zhao, Jiyong; Misra, Ravi; Vosoughi, Aram; Jenks, Scott; Tipton, Christopher; Lund, Frances; Schwartz, George; Goldman, Bruce; Mohan, Chandra; Mehta, Kamal; Mehta, Madhu; Leitgets, Michael; Sanz, Ignacio; Chen, Luojing.
Afiliação
  • Oleksyn D; University of Rochester School of Medicine, 601 Elmwood Avenue, Rochester, NY 14642, USA.
Arthritis Rheum ; 65(4): 1022-31, 2013 Apr.
Article em En | MEDLINE | ID: mdl-23280626
OBJECTIVE: To evaluate the requirement for protein kinase Cß (PKCß) in the development of lupus in mice, and to explore the potential of targeting PKCß as a therapeutic strategy in lupus. METHODS: Congenic mice bearing the disease loci Sle1 or Sle1 and Sle3, which represent different stages of severity in the development of lupus, were crossed with PKCß-deficient mice. The effect of PKCß deficiency in lupus development was analyzed. In addition, the effects of the PKCß-specific inhibitor enzastaurin on the survival of B cells from mice with lupus and human 9G4-positive B cells as well as the in vivo effect of enzastaurin treatment on the development of lupus in Sle mice were investigated. RESULTS: In Sle mice, PKCß deficiency abrogated lupus-associated phenotypes, including high autoantibody levels, proteinuria, and histologic features of lupus nephritis. Significant decreases in spleen size and in the peritoneal B-1 cell population, reduced numbers of activated CD4 T cells, and normalized CD4:CD8 ratios were observed. PKCß deficiency induced an anergic B cell phenotype and preferentially inhibited autoreactive plasma cells and autoantibodies in mice with lupus. Inhibition of PKCß enhanced apoptosis of both B cells from Sle mice and human autoreactive B cells (9G4 positive). Treatment of Sle mice with the PKCß-specific inhibitor enzastaurin prevented the development of lupus. CONCLUSION: This study identifies PKCß as a central mediator of lupus pathogenesis, suggesting that PKCß represents a promising therapeutic target for the treatment of systemic lupus erythematosus. Moreover, the results indicate the feasibility of using a PKCß inhibitor for the treatment of lupus.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteína Quinase C / Linfócitos B / Inibidores de Proteínas Quinases / Indóis / Lúpus Eritematoso Sistêmico Limite: Animals / Humans Idioma: En Ano de publicação: 2013 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteína Quinase C / Linfócitos B / Inibidores de Proteínas Quinases / Indóis / Lúpus Eritematoso Sistêmico Limite: Animals / Humans Idioma: En Ano de publicação: 2013 Tipo de documento: Article