フクイ　トシロウ   FUKUI TOSHIRO   福井　寿朗    所属   関西医科大学  内科学第三講座    職種   准教授
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