title: Toll-like receptor 2 mediates peripheral nerve injury-induced NADPH oxidase 2 expression in spinal cord microglia.
abstract: We have previously reported that NADPH oxidase 2 (Nox2) is up-regulated in spinal cord microglia after spinal nerve injury, demonstrating that it is critical for microglia activation and subsequent pain hypersensitivity. However, the mechanisms and molecules involved in Nox2 induction have not been elucidated. Previous studies have shown that Toll-like receptors (TLRs) are involved in nerve injury-induced spinal cord microglia activation. In this study, we investigated the role of TLR in Nox2 expression in spinal cord microglia after peripheral nerve injury. Studies using TLR knock-out mice have shown that nerve injury-induced microglial Nox2 up-regulation is abrogated in TLR2 but not in TLR3 or -4 knock-out mice. Intrathecal injection of lipoteichoic acid, a TLR2 agonist, induced Nox2 expression in spinal cord microglia both at the mRNA and protein levels. Similarly, lipoteichoic acid stimulation induced Nox2 expression and reactive oxygen species production in primary spinal cord glial cells in vitro. Studies on intracellular signaling pathways indicate that NF-κB and p38 MAP kinase activation is required for TLR2-induced Nox2 expression in glial cells. Conclusively, our data show that TLR2 mediates nerve injury-induced Nox2 gene expression in spinal cord microglia via NF-κB and p38 activation and thereby may contribute to spinal cord microglia activation.
authors: Department of Neuroscience and Physiology, Dental Research Institute, and Brain Korea 21, School of Dentistry, Seoul National University, Seoul 110-799, Korea; Interdisciplinary Program in Neuroscience, College of Natural Science, Seoul National University, Seoul 110-799, Korea.
authors: Hyoungsub
authors: H
authors: Lim
authors: Department of Neuroscience and Physiology, Dental Research Institute, and Brain Korea 21, School of Dentistry, Seoul National University, Seoul 110-799, Korea.
authors: Donghoon
authors: D
authors: Kim
authors: Department of Neuroscience and Physiology, Dental Research Institute, and Brain Korea 21, School of Dentistry, Seoul National University, Seoul 110-799, Korea; Interdisciplinary Program in Neuroscience, College of Natural Science, Seoul National University, Seoul 110-799, Korea. Electronic address: sjlee87@snu.ac.kr.
authors: Sung Joong
authors: SJ
authors: Lee
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D015971:Gene Expression Regulation, Enzymologic; D007150:Immunohistochemistry / Q000379:methods; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017628:Microglia / Q000378:metabolism*; D008954:Models, Biological; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D059348:Peripheral Nerve Injuries / Q000378:metabolism*; D017382:Reactive Oxygen Species; D015398:Signal Transduction; D013116:Spinal Cord / Q000378:metabolism*; D051195:Toll-Like Receptor 2 / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D008562:Membrane Glycoproteins; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D051195:Toll-Like Receptor 2; C488842:Cybb protein, mouse; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; D048051:p38 Mitogen-Activated Protein Kinases
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