%0 Journal Article %A Wen-Yan Cui %A Shufang Zhao %A Renata Polanowska-Grabowska %A Ju Wang %A Jinxue Wei %A Bhagirathi Dash %A Sulie L. Chang %A Jeffrey J. Saucerman %A Jun Gu %A Ming D. Li %T Identification and Characterization of Poly(I:C)-induced Molecular Responses Attenuated by Nicotine in Mouse Macrophages %D 2013 %R 10.1124/mol.112.081497 %J Molecular Pharmacology %P 61-72 %V 83 %N 1 %X To further our understanding of the effects of nicotine on the molecular responses of macrophages during virus or virus-like infections, poly(I:C)-stimulated macrophage-like RAW264.2 cells or mouse primary peritoneal macrophages were challenged with nicotine; and their molecular responses were evaluated using a qRT-PCR array, antibody array, ELISA, Western blotting, and Ca2+ imaging. Of 51 genes expressed in the Toll-like receptor (TLR) and RIG-I-like receptor (RLR) pathways, mRNA expression of 15 genes in RAW264.7 cells was attenuated by nicotine, of which mRNA expression of IL-6, TNF-α, and IL-1β was confirmed to be attenuated in peritoneal macrophages. Concurrently, nicotine treatment attenuated the release of IL-6 and TNF-α from poly(I:C)-stimulated macrophages. However, when poly(I:C)-stimulated macrophages were challenged with nicotine plus α-bungarotoxin (α-BTX), secretion of IL-6 and TNF-α was found to be in a level seen with poly(I:C) stimulation only, indicating that α7-nAChR, a highly Ca2+ permeable ion channel sensitive to blockade by α-BTX, is involved in this process. Furthermore, results from an antibody array indicated that nicotine treatment attenuated the phosphorylation of 82 sites, including Thr286 on CaMKIIα, from poly(I:C)-stimulated RAW264.7 cells, of which 28 are expressed in the downstream cascade of Ca2+ signaling. Coincidentally, poly(I:C)-stimulated macrophages showed attenuated expression of phosphorylated CaMKIIα when pretreated with nicotine. In addition, nicotine attenuated intracellular Ca2+ signal from poly(I:C)-stimulated RAW264.7 cells. Collectively, these results indicate that poly(I:C)-induced molecular responses of macrophages could be significantly attenuated by nicotine. %U https://molpharm.aspetjournals.org/content/molpharm/83/1/61.full.pdf