title: Tumor suppressor p53 inhibits autoimmune inflammation and macrophage function.
abstract: The tumor suppressor p53 regulates apoptosis, cell cycle, and oncogenesis. To explore the roles of p53 in autoimmunity, we studied type 1 diabetes and innate immune responses using C57BL/6 mice deficient in p53. We found that p53-deficient mice were more susceptible to streptozotocin-induced diabetes than control mice, and they produced higher levels of interleukin-1, -6, and -12. The innate immune response of p53-/- macrophages to lipopolysaccharides and gamma-interferon was significantly enhanced compared with p53+/+ cells. p53-/- macrophages produced more proinflammatory cytokines and higher levels of total and phosphorylated signal transducer and activator of transcription (STAT)-1. These results indicate that p53 inhibits autoimmune diabetes and innate immune responses through downregulating STAT-1 and proinflammatory cytokines.
authors.affiliation: 614 BRB-II/III, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, 421 Curie Blvd., Philadelphia, PA 19104, USA.
authors.forename: Shi-Jun
authors.initials: SJ
authors.lastname: Zheng
authors.forename: Salah-Eddine
authors.initials: SE
authors.lastname: Lamhamedi-Cherradi
authors.forename: Pu
authors.initials: P
authors.lastname: Wang
authors.forename: Lingyun
authors.initials: L
authors.lastname: Xu
authors.forename: Youhai H
authors.initials: YH
authors.lastname: Chen
mesh_terms: D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics; D007249:Inflammation / Q000276:immunology* / Q000517:prevention & control; D018664:Interleukin-12 / Q000097:blood; D007515:Islets of Langerhans / Q000276:immunology / Q000473:pathology; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D050794:STAT1 Transcription Factor; D015534:Trans-Activators / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
chemical_list: D004268:DNA-Binding Proteins; D050794:STAT1 Transcription Factor; C494080:Stat1 protein, mouse; D015534:Trans-Activators; D016159:Tumor Suppressor Protein p53; D018664:Interleukin-12