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Novel role of nicotinic acetylcholine receptor‐dependent signaling in macrophage survival
Author(s) -
Tano JeanYves K,
Vazquez Guillermo
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.lb446
Subject(s) - macrophage , apoptosis , nicotinic agonist , signal transduction , microbiology and biotechnology , receptor , cholinergic , annexin , tunel assay , acetylcholine receptor , protein kinase b , cancer research , chemistry , biology , endocrinology , biochemistry , in vitro
Atherosclerosis is a maladaptive inflammatory response of the arterial wall in which an imbalance between survival and apoptosis of lesional macrophages plays a dominant role. Reduced macrophage apoptosis in the early atherogenic stages increases lesion cellularity and volume and promotes lesion progression. Recent studies depict nicotinic acetylcholine receptors (nAchRs) as epicenters of an anti‐inflammatory response that targets lesional macrophages, but the signaling mechanisms associated with this process remain poorly understood. To gather preliminary insight into a potential link between macrophage nAchRs and signaling mechanisms involved in macrophage survival/apoptosis, we undertook a biochemical/pharmacological approach to study activation status of survival molecules in PMA‐differentiated THP‐1 macrophages (TDMs). Our studies show that treatment of TDMs with cholinergic agonists results in phosphorylation of AKT and IkBα, two critical pathways in regulation of macrophage survival. This effect is recapitulated by agonists that specifically activate nAchRs suggesting that pro‐survival signaling occurs downstream those receptors. Evaluation of macrophage apoptosis (by TUNEL and Annexin V binding assays) will determine if nAchR‐dependent survival signaling translates into reduced macrophage apoptosis. Supported by UT COM & AHA (SDG0635250N to GV)