Enhanced production of IL-17A during zymosan-induced peritonitis in obese mice
Enhanced production of IL-17A during zymosan-induced peritonitis in obese mice
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DOI：
10.1189/jlb.0309188
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发表时间：
2010-01-01
影响因子：
5.5
通讯作者：
Fantuzzi, Giamila
中科院分区：
文献类型：
--
作者：
Pini, Maria;Fantuzzi, Giamila
IL-17 A是一种对宿主防御至关重要的促炎细胞因子，并参与自身免疫性疾病的发病机制。肥胖与慢性低度炎症有关，但也与急性炎症反应有关。我们使用ZY诱导的腹膜炎模型研究了肥胖对IL-17 A产生的影响。与瘦对照组相比，ZY给药诱导肥胖瘦素缺乏ob/ob小鼠和饮食诱导肥胖（DIO）小鼠的炎症反应显著加剧。与瘦型动物相比，ob/ob和DIO小鼠腹腔液中IL-17 A水平响应ZY显著升高。重组的ob/ob小鼠与外源性瘦素没有改变IL-17 A的生产显着响应ZY。与瘦小鼠相比，从ZY注射肥胖小鼠获得的腹膜细胞和脂肪组织表达显著更高水平的IL-17 A mRNA。注射ZY的肥胖小鼠的腹膜Ly 6 G（+）中性粒细胞中约有2%表达IL-17 A蛋白，而瘦小鼠的细胞中只有0.2%表达IL-17 A蛋白。在ob/ob小鼠中中和IL-17可抑制中性粒细胞募集和嗜中性粒细胞吸引性CXC趋化因子和IL-6的产生，而不影响巨噬细胞浸润或IL-10和趋化因子CCL 2的水平。相反，中和IL-6不影响IL-17 A或趋化因子的产生，同时显著减少急性期蛋白血清淀粉样蛋白A的产生。这些数据表明，在急性炎症期间，肥胖小鼠中嗜中性粒细胞衍生的IL-17 A增加，并有助于炎症反应的恶化。J. Leukoc. 87：51-58; 2010.
IL-17A is a proinflammatory cytokine critical for host defense and involved in the pathogenesis of autoimmune disorders. Obesity is associated with chronic low-grade inflammation but also with a heightened acute inflammatory response. We investigated the effect of obesity on IL-17A production using the model of ZY-induced peritonitis. Compared with lean controls, administration of ZY induced a significantly exacerbated inflammatory response in obese leptin-deficient ob/ob mice and in mice with diet-induced obesity (DIO). Levels of IL-17A in the peritoneal fluid in response to ZY were elevated significantly in ob/ob and DIO mice compared with lean animals. Reconstitution of ob/ob mice with exogenous leptin did not alter production of IL-17A significantly in response to ZY. Peritoneal cells and adipose tissue obtained from ZY-injected obese mice expressed significantly higher levels of IL-17A mRNA compared with lean mice. Approximately 2% of peritoneal Ly6G(+) neutrophils from ZY-injected obese mice expressed IL-17A protein, compared with 0.2% of cells obtained from lean mice. Neutralization of IL-17 in ob/ob mice inhibited neutrophil recruitment and production of neutrophil-attracting CXC chemokines and IL-6, without affecting macrophage infiltration or levels of IL-10 and the chemokine CCL2. In contrast, neutralization of IL-6 did not affect production of IL-17A or chemokines while reducing production of the acute-phase protein serum amyloid A significantly. These data demonstrate that neutrophil-derived IL-17A is increased in obese mice during acute inflammation and contributes to exacerbation of inflammatory responses. J. Leukoc. Biol. 87: 51-58; 2010.