signature=c70e560882b77ff7fa91db2d39495f36,IL-17 neutralization significantly ameliorates hepatic gr...

摘要：

IL-17(also referred to IL-17A)is a signature cytokine of Th17 cells implicated in the induction and progression of chronic inflammatory diseases.Several studies in the low-pathology Schistosoma mansoni(S.mansoni)-infected C57BL/6 mice,immunized with soluble schistosome egg Ags(SEA)in complete Freund's adjuvant(CFA),have shown that severe hepatic granulomatous inflammation correlated with high levels of IL-17.To investigate whether IL17 is up-regulated in Schistosoma japonicum-infected mice and the involvement of the cytokine in the development of egg-induced granuloms.C57BL/6 mice were infected with 20±2 cercariae of S.japonicum and sacrificed biweekly after infection for a total of 12wk.IL-17 m RNA expression in the livers was analyzed by RT-q PCR and IL-17 protein in the liver homogenates was detected by ELISA.Some C57BL/6 mice were administrated by a tail vein injection with 50μg of neutralizing anti-mouse-IL17 m Ab(clone 50104,R&D Systems)or isotype-matched rat Ig G2a m Ab(R&D Systems)starting at 24,28,32,36 and 40 days after infection,and sacrificed 48 h later after the last antibody administration.Sections stained with HE for assessment of hepatic pathology.Our results showed that IL-17 expression was elevated during the course of infection.The temporal expression of IL-17 and cytokines/chemokines downstream of its signaling paralleled hepatic granulomatous inflammation.Treatment of S.japonicum-infected mice with IL-17-neutralizing m Ab resulted in significant down-modulation of granulomatous inflammation and hepatocyte necrosis.The protection was associated with less expression of proinflammatory cytokines/chemokines,such as IL-6,CXCL1 and CXCL2 and a reduced number of infiltrating neutrophils.Cultured granuloma cells from anti-IL-17 treated mice released less IFN-g and IL-4 than those of control mice.Our data indicated the pathogenic role of IL-17 in hepatic immunopathology in S.japonicum-infected mice.Anti-IL-17 m Ab could significantly ameliorate hepaticgranulomatous inflammation,partly through down-regulation of proinflammatory cytokines/chemokines and recruitment of neutrophils.

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