Abstract 212: Card9-mediated Signaling is Critical to Cytokine Production in Mice With PM Exposure

Abstract

Oxidative stress and inflammation are considered an important mechanism for the development of cardiovascular diseases. Cytokines including interleukin (IL)-6 and tumor necrosis factor-α (TNF-α) play an important role in oxidative stress and inflammation. It is known that ambient fine particulate matter ( PM ) exposure is closely associated with cardiovascular diseases and oxidative stress. Caspase-recruitment domain 9 ( Card9 ) signaling is critically involvement in the function of macrophages, neutrophils and monocytes that are important for oxidative stress and inflammation. The present study was designed to evaluate the role of CARD9-mediated signaling in cytokines production in mice with PM exposure. Both male wild-type (WT) C57BL/6 mice (8-10 weeks) and age-matched CARD9 knockout (KO) mice (with C57BL/6 background) were exposed to PM2.5 for 6 weeks via intranasal approach with PBS as the control. Serum concentrations of the cytokines including IL-6, IL-1β, and TNF-α were measured with ELISA in the mice before and after PM exposure. There was no difference in the serum levels of IL-6, IL-1β, or TNF-α between WT mice and CARD9 KO mice exposed to PBS. As expected, PM exposure substantially increased the serum levels of IL-6, IL-1β, and TNF-α in the WT mice (by up to 6 times). However, no significant increase in the serum concentrations for IL-6, IL-1β, and TNF-α was observed in CARD9 KO mice exposed to PM. Increased inflammatory infiltrations in the lungs were observed in the WT mice as compared to the CARD9 KO mice with PM exposure. In conclusion, the present study demonstrated that increased cytokines were produced in WT mice, but not in CARD9 KO mice with PM exposure. The data suggested that CARD9 signaling played a critical role in the production of inflammatory cytokines in the mice in response to PM exposure, and might contribute to the development of cardiovascular diseases related to PM exposure.