IL-18 enhances IFN-gamma-induced production of CXCL9, CXCL10, and CXCL11 in human keratinocytes.
IL-18 enhances IFN-gamma-induced production of CXCL9, CXCL10, and CXCL11 in human keratinocytes.
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发表时间：
2007
影响因子：
5.4
通讯作者：
N. Kanda;Teruo Shimizu;Y. Tada;Shinichi Watanabe
中科院分区：
文献类型：
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作者：
N. Kanda;Teruo Shimizu;Y. Tada;Shinichi Watanabe
IL-18参与特应性皮炎、牛皮癣和过敏性接触性皮炎的发病机制。 CXCL9、CXCL10 和 CXCL11 招募 1 型 T 细胞，并且在这些皮肤病中角质形成细胞产生的这些趋化因子得到增强。我们检测了 IL-18 对 IFN-γ 诱导的人角质形成细胞中 CXCL9、CXCL10 和 CXCL11 产生的体外影响。 IL-18 增强 IFN-γ 诱导的 CXCL9、CXCL10 和 CXCL11 的分泌和 mRNA 表达，同时激活 NF-κB、STAT1 和 IFN 调节因子 (IRF)-1。针对 NF-kappaB p50、p65 或 STAT1 的反义寡核苷酸抑制 CXCL9、CXCL10 和 CXCL11 的产生，反义 IRF-1 抑制 CXCL11 的产生。 PI3 K、p38 MAPK 和 MEK 抑制剂可抑制 IL-18 加 IFN-gamma 诱导的 CXCL9、CXCL10 和 CXCL11 产生以及 NF-kappaB、STAT1 和 IRF-1 活性。 IL-18 诱导 ERK 和 Akt 磷酸化，而 IFN-γ 诱导 p38 MAPK 磷酸化。这些结果表明，IL-18 可能通过 PI3 K/Akt 和 MEK/ERK 途径激活 NF-kappaB、STAT1 或 IRF-1，从而增强 IFN-γ 诱导的角质形成细胞中 CXCL9、CXCL10 和 CXCL11 的产生。 IL-18 的这些作用可能会促进 1 型 T 细胞浸润到炎症性皮肤病病变部位并加剧皮肤炎症。 IL-18 可能在这些皮肤病中充当促炎细胞因子，因此是候选治疗靶点。
IL-18 is involved in the pathogenesis of atopic dermatitis, psoriasis, and allergic contact dermatitis. CXCL9, CXCL10, and CXCL11 recruit type 1 T cells, and the production of these chemokines by keratinocytes is enhanced in these dermatoses. We examined the in vitro effects of IL-18 on IFN-gamma-induced CXCL9, CXCL10, and CXCL11 production in human keratinocytes. IL-18 enhanced the IFN-gamma-induced secretion and mRNA expression of CXCL9, CXCL10, and CXCL11 in parallel to the activation of NF-kappaB, STAT1, and IFN-regulatory factor (IRF)-1. Antisense oligonucleotides against NF-kappaB p50, p65, or STAT1 suppressed CXCL9, CXCL10, and CXCL11 production, and antisense IRF-1 suppressed CXCL11 production. Inhibitors of PI3 K, p38 MAPK, and MEK suppressed IL-18 plus IFN-gamma-induced CXCL9, CXCL10, and CXCL11 production and NF-kappaB, STAT1, and IRF-1 activities. IL-18 induced phosphorylation of ERK and Akt, while IFN-gamma induced phosphorylation of p38 MAPK. These results suggest that IL-18 may potentiate IFN-gamma-induced CXCL9, CXCL10, and CXCL11 production in keratinocytes by activating NF-kappaB, STAT1, or IRF-1 through PI3 K/Akt and MEK/ERK pathways. These effects of IL-18 may promote the infiltration of type 1 T cells into lesions with inflammatory dermatoses and amplify the skin inflammation. IL-18 may act as a pro-inflammatory cytokine in these dermatoses and thus is a candidate therapeutic target.