Enhanced production of IL-17A during zymosan-induced peritonitis in obese mice.
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.
Pini
Maria
M
Department of Kinesiology, University of Illinois, Chicago, IL 60612, USA.
Fantuzzi
Giamila
G
D000208:Acute Disease; D000818:Animals; D001202:Ascitic Fluid / Q000378:metabolism; D019743:Chemokines, CXC / Q000096:biosynthesis / Q000235:genetics; D004041:Dietary Fats / Q000633:toxicity; D005260:Female; D005786:Gene Expression Regulation; D007249:Inflammation; D020381:Interleukin-17 / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D050152:Intra-Abdominal Fat / Q000378:metabolism; D020738:Leptin / Q000172:deficiency / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D009504:Neutrophils / Q000378:metabolism*; D009765:Obesity / Q000150:complications*; D010538:Peritonitis / Q000139:chemically induced / Q000150:complications / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000378:metabolism; D013851:Thinness / Q000378:metabolism; D015054:Zymosan / Q000633:toxicity; D000093242:Interleukin-6 Inhibitors
D019743:Chemokines, CXC; D004041:Dietary Fats; D020381:Interleukin-17; D020738:Leptin; D015054:Zymosan; D000093242:Interleukin-6 Inhibitors; C098680:Il17a protein, mouse