title: The role of TRPM2 in hydrogen peroxide-induced expression of inflammatory cytokine and chemokine in rat trigeminal ganglia.
abstract: Trigeminal ganglia (TG) contain neuronal cell bodies surrounded by satellite glial cells. Although peripheral injury is well known to induce changes in gene expression within sensory ganglia, detailed mechanisms whereby peripheral injury leads to gene expression within sensory ganglia are not completely understood. Reactive oxygen species (ROS) are an important modulator of hyperalgesia, but the role of ROS generated within sensory ganglia is unclear. Since ROS are known to affect transcription processes, ROS generated within sensory ganglia could directly influence gene expression and induce cellular changes at the soma level. In this study, we hypothesized that peripheral inflammation leads to cytokine and chemokine production and ROS generation within TG and that transient receptor potential melastatin (TRPM2), a well known oxidative sensor, contributes to ROS-induced gene regulation within TG. The masseter injection of complete Freund's adjuvant (CFA) resulted in a significantly elevated level of ROS within TG of the inflamed side with a concurrent increase in cytokine expression in TG. Treatment of TG cultures with H2O2 significantly up-regulated mRNA and protein levels of cytokine/chemokine such as interleukin 6 (IL-6) and chemokine (C-X-C motif) ligand 2 (CXCL2). TRPM2 was expressed in both neurons and non-neuronal cells in TG, and pretreatment of TG cultures with 2-aminoethoxydiphenyl borate (2-APB), an inhibitor of TRPM2, or siRNA against TRPM2 attenuated H2O2-induced up-regulation of IL-6 and CXCL2. These results suggested that activation of TRPM2 could play an important role in the modulation of cytokine/chemokine expression within TG under oxidative stress and that such changes may contribute to amplification of nociceptive signals leading to pathological pain conditions.
authors: University of Maryland School of Dentistry, Department of Neural and Pain Sciences, Program in Neuroscience, United States.
authors: M-K
authors: MK
authors: Chung
authors: University of Maryland School of Dentistry, Department of Neural and Pain Sciences, Program in Neuroscience, United States.
authors: J
authors: J
authors: Asgar
authors: University of Maryland School of Dentistry, Department of Neural and Pain Sciences, Program in Neuroscience, United States.
authors: J
authors: J
authors: Lee
authors: University of Maryland School of Dentistry, Department of Neural and Pain Sciences, Program in Neuroscience, United States.
authors: M S
authors: MS
authors: Shim
authors: University of Maryland School of Dentistry, Department of Neural and Pain Sciences, Program in Neuroscience, United States.
authors: C
authors: C
authors: Dumler
authors: University of Maryland School of Dentistry, Department of Neural and Pain Sciences, Program in Neuroscience, United States. Electronic address: jro@umaryland.edu.
authors: J Y
authors: JY
authors: Ro
mesh_terms: D000818:Animals; D001896:Boron Compounds / Q000627:therapeutic use; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D005620:Freund's Adjuvant / Q000633:toxicity; D007839:Functional Laterality; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism*; D008297:Male; D009457:Neuroglia / Q000187:drug effects; D009474:Neurons / Q000187:drug effects; D016877:Oxidants / Q000494:pharmacology*; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D050053:TRPM Cation Channels / Q000378:metabolism*; D012668:Trigeminal Ganglion / Q000166:cytology / Q000187:drug effects*
chemical_list: D001896:Boron Compounds; D016207:Cytokines; D016877:Oxidants; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D050053:TRPM Cation Channels; C557080:Trpm2 protein, rat; D005620:Freund's Adjuvant; D006861:Hydrogen Peroxide; C109986:2-aminoethoxydiphenyl borate; D010751:Phosphopyruvate Hydratase
keywords: CXCL2; IL-6; myositis; oxidative stress; satellite glial cells