論文種別	原著(症例報告除く)
言語種別	英語
査読の有無	査読あり
表題	The Role of Innate Immunity in the Pathogenesis of Experimental Autoimmune Pancreatitis in Mice.
掲載誌名	正式名：Pancreas 略　 称：Pancreas ISSNコード：08853177/15364828
巻・号・頁	40(1),pp.95-102
著者・共著者	Nishio A, Asada M, Uchida K, Fukui T, Chiba T, Okazaki K
発行年月	2011/01
概要	OBJECTIVE:To determine the role of innate immunity in the development of autoimmune pancreatitis in mice induced by toll-like receptor (TLR) stimulation. METHODS:Six-week-old female MRL/Mp mice were injected intraperitoneally with polyinosinic polycytidylic acid (poly I:C) or lipopolysaccharide (LPS) at doses of 5 mg/kg body weight twice weekly for 12 weeks. The mice were killed, and the severity of pancreatitis was graded using a histological scoring system. Serum cytokine levels of mice with pancreatitis and mice that were given a single injection of TLR ligands were measured using enzyme-linked immunosorbent assays. The effect of TLR stimulation on the development of pancreatitis was also examined using C57BL/6 interleukin (IL)-10-deficient mice. RESULTS:Administration of poly I:C accelerated the development of pancreatitis in MRL/Mp mice, but LPS did not. Serum levels of IL-10 and IL-12 were significantly elevated in mice with autoimmune pancreatitis. A single injection of LPS markedly increased serum levels of interferon-γ, tumor necrosis factor-α, IL-10, and IL-12 compared with those of poly I:C-treated mice. Treatment with not only poly I:C but also LPS induced pancreatitis in IL-10-deficient mice but not in wild-type mice. CONCLUSION:Repeated stimulation of innate immunity induces autoimmunity in the pancreas of mice via an imbalance between proinflammatory and anti-inflammatory cytokines.
DOI	10.1097/MPA.0b013e3181f3a5d4
文献番号	20881901