Nicotine induces P2X4 receptor, interleukin-1 beta, and brain-derived neurotrophic factor expression in BV2 microglia cells. Issue 18 (16th December 2020)

• Record Type: Journal Article
• Authors: Guo, Lina; Zhang, Yang; Lv, Qing; Zhang, Zongwang
• Is Part Of: NeuroReport. Volume 31:Issue 18(2020)
• Publication Date: 2020-12-16
• Subjects: BDNF -- IRF8 -- nicotine -- microglia -- pain -- P2X4 receptor; Neurosciences -- Periodicals; Nervous system -- Periodicals; Neurophysiology -- Periodicals; Nervous System Diseases -- Periodicals; Nervous System Physiological Phenomena -- Periodicals; Neurosciences -- Periodicals; 616.805
• DOI: 10.1097/WNR.0000000000001546
• Languages: English
• ISSNs: 0959-4965

Abstract

Abstract : Objective: Upregulation of P2X4 receptor (P2X4R), brain-derived neurotrophic factor (BDNF), and interleukin-1 beta (IL-1β) in activated microglia is associated with hyperalgesia. This study investigated whether nicotine increases pain hypersensitivity by altering the expression of these molecules in microglia. We also examined the role of interferon regulatory factor 8 (IRF8) in this process. Methods: Experiments were performed in BV2 microglial cells. IRF8 was knocked down or overexpressed using lentiviruses harboring a short hairpin RNA targeting IRF8 or an IRF8 overexpression construct, respectively. P2X4R, BDNF, and IL-1β mRNA and protein levels were evaluated by real-time PCR and western blotting, respectively, and BDNF and IL-1β secretion was assessed by ELISA. Results: Chronic nicotine exposure enhanced the expression of P2X4R, BDNF, and IL-1β in BV2 cells, and stimulated the release of BDNF and IL-1β in the presence of ATP. IRF8 was found to mediate the nicotine-induced increases in BDNF and IL-1β mRNA and P2X4R protein levels in BV2 cells. Conclusion: Nicotine may increase pain hypersensitivity by promoting the expression of P2X4R, BDNF, and IL-1β through modulation of IRF8 levels in microglial cells.