title: IL-17A synergizes with IFN-γ to upregulate iNOS and NO production and inhibit chlamydial growth.
abstract: IFN-γ-mediated inducible nitric oxide synthase (iNOS) expression is critical for controlling chlamydial infection through microbicidal nitric oxide (NO) production. Interleukin-17A (IL-17A), as a new proinflammatory cytokine, has been shown to play a protective role in host defense against Chlamydia muridarum (Cm) infection. To define the related mechanism, we investigated, in the present study, the effect of IL-17A on IFN-γ induced iNOS expression and NO production during Cm infection in vitro and in vivo. Our data showed that IL-17A significantly enhanced IFN-γ-induced iNOS expression and NO production and inhibited Cm growth in Cm-infected murine lung epithelial (TC-1) cells. The synergistic effect of IL-17A and IFN-γ on Chlamydia clearance from TC-1 cells correlated with iNOS induction. Since one of the main antimicrobial mechanisms of activated macrophages is the release of NO, we also examined the inhibitory effect of IL-17A and IFN-γ on Cm growth in peritoneal macrophages. IL-17A (10 ng/ml) synergizes with IFN-γ (200 U/ml) in macrophages to inhibit Cm growth. This effect was largely reversed by aminoguanidine (AG), an iNOS inhibitor. Finally, neutralization of IL-17A in Cm infected mice resulted in reduced iNOS expression in the lung and higher Cm growth. Taken together, the results indicate that IL-17A and IFN-γ play a synergistic role in inhibiting chlamydial lung infection, at least partially through enhancing iNOS expression and NO production in epithelial cells and macrophages.
authors: Department of Immunology, Tianjin Key Laboratory of Cellular and Molecular Immunology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.
authors: Yongci
authors: Y
authors: Zhang
authors: Haiping
authors: H
authors: Wang
authors: Jianyun
authors: J
authors: Ren
authors: Xiaofei
authors: X
authors: Tang
authors: Ye
authors: Y
authors: Jing
authors: Donghong
authors: D
authors: Xing
authors: Guosheng
authors: G
authors: Zhao
authors: Zhi
authors: Z
authors: Yao
authors: Xi
authors: X
authors: Yang
authors: Hong
authors: H
authors: Bai
mesh_terms: D000818:Animals; D002460:Cell Line; D002690:Chlamydia Infections / Q000188:drug therapy* / Q000378:metabolism; D023502:Chlamydia muridarum / Q000187:drug effects / Q000472:pathogenicity; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology* / Q000627:therapeutic use*; D020381:Interleukin-17 / Q000494:pharmacology* / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D020381:Interleukin-17; D009569:Nitric Oxide; D007371:Interferon-gamma; D052247:Nitric Oxide Synthase Type II