Damaged Neuronal Cells Induce Inflammatory Gene Expression in Schwann Cells: Implication in the Wallerian Degeneration
2
조회
0
다운로드
0
인용
0
참고문헌
초록
Abstract
Schwann cells play an important role in peripheral nerve regeneration. Upon nerve injury, Schwann cells are activated and produce various proinflammatory mediators including IL-6, LIF and MCP-1, which result in the recruitment of macrophages and phagocytosis of myelin debris. However, it is unclear how the nerve injury induces Schwann cell activation. Recently, it was reported that necrotic cells induce immune cell activation via toll-like receptors (TLRs). This suggests that the TLRs expressed on Schwann cells may recognize nerve damage by binding to the endogenous ligands secreted by the damaged nerve, thereby inducing Schwann cell activation. To explore the possibility, we stimulated iSC, a rat Schwann cell line, with damaged neuronal cell extracts (DNCE). The stimulation of iSC with DNCE induced the expression of various inflammatory mediators including IL-6, LIF, MCP-1 and iNOS. Studies on the signaling pathway indicate that NF-B, p38 and JNK activation are required for the DNCE-induced inflammatory gene expression. Furthermore, treatment of either anti-TLR3 neutralizing antibody or ribonuclease inhibited the DNCE-induced proinflammatory gene expression in iSC. In summary, these results suggest that damaged neuronal cells induce inflammatory Schwann cell activation via TLR3, which might be involved in the Wallerian degeneration after a peripheral nerve injury.
참고문헌 (27)
- "Pathogenesis of influenza virus-induced pneumonia involvement of both nitric oxide and oxygen radicals", 93, pp.2448~2453 (1996)
- "Isolation of activated adult Schwann cells and a spontaneously immortal Schwann cell clone", pp.231~238 (1992)
- "Interleukin-6 production by Schwann cells and induction in sciatic nerve injury", 64, pp.850~858 (1995)
- "Cloning and characterization of a sub-family of human toll-like receptors", 11, pp.372~378 (2000)
- "Inducible nitric oxide synthase (iNOS) in immune-mediated demyeli-nation and Wallerian degeneration of the rat peripheral nervous system", 187, pp.350~358 (2004)
- "Nitric oxide in neuronal dege-neration", 211, pp.33~40 (1996)
- "Neurochemical characteristics of a novel dorsal root ganglion X neuroblastoma hybrid cell line", pp.1624~11 1631 (1987)
- "The cellular and molecular basis of peripheral nerve regeneration", 14, pp.67~116 (1997)
- "Myelin-associated inhi-bitors of axon regeneration", 74, pp.479~485 (2003)
- "A Toll-like receptor recognizes bacterial DNA", 408, pp.740~745 (2000)
- "Microglial activation and amyloid-beta clearance induced by exogenous heat-shock proteins", 16, pp.601~613 (2002)
- "mRNA is an endogenous ligand for Toll-like receptor 3", 279, pp.12542~12550 (2004)
- "Double-stranded RNA induces inflammatory gene expression in Schwann cells Implication in the Wallerian degeneration", 8, pp.253~257 (2004)
- "Local nitric oxide synthase activity in a model of neuropathic pain", 10, pp.1846~1855 (1998)
- "Local expression of inducible nitric oxide synthase in an animal model of neuropathic pain", 260, pp.207~219 (1999)
- "Increased activation of nuclear factor kappa B in rat lumbar dorsal root ganglion neurons following partial sciatic nerve injuries", 797, pp.243~254 (1998)
- "A human homologue of the Drosophila Toll protein signals activation of adaptive immunity", 388, pp.394~397 (1997)
- "Inhibition of p38 MAP kinase activity enhances axonal regeneration", 184, pp.606~614 (2003)
- "Expression of Toll-like receptor 2 on human Schwann cells a mechanism of nerve damage in leprosy", 71, pp.1427~1433 (2003)
- "Degeneration and regene-ration of the peripheral nervous system from Augustus Waller's observations to neuroinflammation", 7, pp.13~27 (2002)
- "TLR2-deficient and MyD88-deficient mice are highly susceptible to Staphylo-coccus aureus infection", 165, pp.5392~5396 (2000)
- "Peripheral nerve regeneration and neurotrophic factors", 194, pp.1~14 (1999)
- "Denervated Schwann cells attract macrophages by secretion of leukemia inhibitory factor (LIF) and monocyte chemo-attractant protein-1 in a process regulated by interleukin-6 and LIF", 22, pp.6696~6703 (2002)
- "HSP70 as endogenous stimulus of the Toll", interleukin-1 receptor signal pathway, 2002, pp.277, 15107~15112
- "Toll-like receptor that prevents infection by uropathogenic bacteria", 303, pp.1522~1526 (2004)
- "Evidence for nitric oxide and nitric oxide synthase activity in proximal stumps of transected Peripheral nerves", 91, pp.1515~1527 (1999)
- "Evidence for nitric oxide and nitric oxide synthase activity in proximal stumps of transected Peripheral nerves", 91, pp.1515~1527 (1999)