Saturated fatty acids activate the inflammatory signalling pathway in Schwann cells: Implication in sciatic nerve injury.
Schwann cell
inflammatory response
myeloid differentiation protein 2
saturated fatty acid
sciatic nerve injury
toll-like receptor 4
Journal
Scandinavian journal of immunology
ISSN: 1365-3083
Titre abrégé: Scand J Immunol
Pays: England
ID NLM: 0323767
Informations de publication
Date de publication:
Aug 2020
Aug 2020
Historique:
received:
27
01
2020
revised:
21
04
2020
accepted:
14
05
2020
pubmed:
20
6
2020
medline:
31
7
2020
entrez:
20
6
2020
Statut:
ppublish
Résumé
Sciatic nerve injury affects quality of life. Many immune cells and inflammatory cytokines have been reported to be involved in sciatic nerve injury, but little is known about the ligands and receptors that trigger inflammatory responses. By using a modified sciatic nerve clamp injury method, we found that the recruitment of Schwann cells and the inflammatory response were enhanced after sciatic nerve injury. Toll-like receptor 4 (TLR4), one of the major members of the TLR family, is highly expressed in Schwann cells. Under certain conditions, myeloid differentiation protein 2 (MD2) binds to TLR4 on the membrane and plays important roles in the inflammatory response. The reductions in the recruitment of Schwann cells and the inflammatory response induced by the blockade of TLR4 or MD2 suggest that TLR4 and MD2 are involved in sciatic nerve injury. What are the endogenous signals that activate the inflammatory response? A large number of free saturated fatty acids (SFAs) are released from Schwann cells, adipocytes and the blood after sciatic nerve injury. Liang et al reported that Schwann cells can be stimulated by palmitic acid (PA). Here, we found that the expression and secretion of TNF-α and IL-6 were enhanced by PA treatment. Moreover, PA activated TLR4 signalling pathway-related proteins and stimulated a strong association between TLR4 and MD2. Blocking TLR4 or MD2 reversed the PA-induced inflammatory response and TLR4 downstream signalling pathway. Thus, we speculated that SFAs act as endogenous ligands that activate TLR4/MD2, thus triggering Schwann cell inflammation during sciatic nerve injury.
Substances chimiques
Fatty Acids
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e12896Subventions
Organisme : National Natural Science Foundation of China
ID : 81072398
Informations de copyright
© 2020 The Scandinavian Foundation for Immunology.
Références
Pineau I, Lacroix S. Endogenous signals initiating inflammation in the injured nervous system. Glia. 2009;57(4):351-361.
Mueller M, Wacker K, Ringelstein EB, Hickey WF, Imai Y, Kiefer R. Rapid response of identified resident endoneurial macrophages to nerve injury. Am J Pathol. 2001;159(6):2187-2197.
Boivin A, Pineau I, Barrette B, et al. Toll-like receptor signaling is critical for Wallerian degeneration and functional recovery after peripheral nerve injury. J Neurosci. 2007;27(46):12565-12576.
Freria CM, Bernardes D, Almeida GL, Simões GF, Barbosa GO, Oliveira ALR. Impairment of toll-like receptors 2 and 4 leads to compensatory mechanisms after sciatic nerve axotomy. J Neuroinflammation. 2016;13(1):118.
Goethals S, Ydens E, Timmerman V, Janssens S. Toll-like receptor expression in the peripheral nerve. Glia. 2010;58(14):1701-1709.
Shamash S, Reichert F, Rotshenker S. The cytokine network of Wallerian degeneration: tumor necrosis factor-alpha, interleukin-1alpha, and interleukin-1beta. J Neurosci. 2002;22(8):3052-3060.
Lee H, Jo E-K, Choi S-Y, et al. Necrotic neuronal cells induce inflammatory Schwann cell activation via TLR2 and TLR3: implication in Wallerian degeneration. Biochem Biophys Res Commun. 2006;350(3):742-747.
Karanth S, Yang G, Yeh J, Richardson P. Nature of signals that initiate the immune response during Wallerian degeneration of peripheral nerves. Exp Neurol. 2006;202(1):161-166.
Molteni M, Gemma S, Rossetti C. The role of toll-like receptor 4 in infectious and noninfectious inflammation. Mediators Inflamm. 2016;2016:6978936.
Lee H, Lee S, Cho I-H, Lee SJ. Toll-like receptors: sensor molecules for detecting damage to the nervous system. Curr Protein Pept Sci. 2013;14(1):33-42.
Sloane JA, Blitz D, Margolin Z, Vartanian T. A clear and present danger: endogenous ligands of Toll-like receptors. Neuromolecular Med. 2010;12(2):149-163.
Cermenati G, Audano M, Giatti S, et al. Lack of sterol regulatory element binding factor-1c imposes glial Fatty Acid utilization leading to peripheral neuropathy. Cell Metab. 2015;21(4):571-583.
Verheijen MH, Chrast R, Burrola P, Lemke G. Local regulation of fat metabolism in peripheral nerves. Genes Dev. 2003;17(19):2450-2464.
O'Brien PD, Hinder LM, Callaghan BC, Feldman EL. Neurological consequences of obesity. Lancet Neurol. 2017;16(6):465-477.
Wang Z, Liu D, Wang F, et al. Saturated fatty acids activate microglia via Toll-like receptor 4/NF-kappaB signalling. Br J Nutr. 2012;107(2):229-241.
Gupta S, Knight AG, Gupta S, Keller JN, Bruce-Keller AJ. Saturated long-chain fatty acids activate inflammatory signaling in astrocytes. J Neurochem. 2012;120(6):1060-1071.
Kim SJ, Kim HM. Dynamic lipopolysaccharide transfer cascade to TLR4/MD2 complex via LBP and CD14. BMB Rep. 2017;50(2):55-57.
Zhang Y, Wu B, Zhang H, et al. Inhibition of MD2-dependent inflammation attenuates the progression of non-alcoholic fatty liver disease. J Cell Mol Med. 2018;22(2):936-947.
Chen H, Zhang Y, Zhang W, et al. Inhibition of myeloid differentiation factor 2 by baicalein protects against acute lung injury. Phytomedicine. 2019;63:152997.
Wang Y, Shan X, Dai Y, et al. Curcumin analog L48H37 prevents lipopolysaccharide-induced TLR4 signaling pathway activation and sepsis via targeting MD2. J Pharmacol Exp Ther. 2015;353(3):539-550.
Wang Y, Qian Y, Fang Q, et al. Saturated palmitic acid induces myocardial inflammatory injuries through direct binding to TLR4 accessory protein MD2. Nat Commun. 2017;8:13997.
Huang S, Rutkowsky JM, Snodgrass RG, et al. Saturated fatty acids activate TLR-mediated proinflammatory signaling pathways. J Lipid Res. 2012;53(9):2002-2013.
Harpio R, Einarsson R. S100 proteins as cancer biomarkers with focus on S100B in malignant melanoma. Clin Biochem. 2004;37(7):512-518.
Abdo H, Calvo-Enrique L, Lopez JM, et al. Specialized cutaneous Schwann cells initiate pain sensation. Science. 2019;365(6454):695-699.
Geuna S, Raimondo S, Ronchi G, et al. Chapter 3: histology of the peripheral nerve and changes occurring during nerve regeneration. Int Rev Neurobiol. 2009;87:27-46.
Rydevik B, Lundborg G. Permeability of intraneural microvessels and perineurium following acute, graded experimental nerve compression. Scand J Plast Reconstr Surg. 1977;11(3):179-187.
Tappia PS, Man WJ, Grimble RF. Influence of unsaturated fatty acids on the production of tumour necrosis factor and interleukin-6 by rat peritoneal macrophages. Mol Cell Biochem. 1995;143(2):89-98.
Laine PS, Schwartz EA, Wang Y, et al. Palmitic acid induces IP-10 expression in human macrophages via NF-kappaB activation. Biochem Biophys Res Commun. 2007;358(1):150-155.
Martins de Lima-Salgado T, Coccuzzo Sampaio S, Cury-Boaventura MF, Curi R. Modulatory effect of fatty acids on fungicidal activity, respiratory burst and TNF-alpha and IL-6 production in J774 murine macrophages. Br J Nutr. 2011;105(8):1173-1179.
Averill MM, Bornfeldt KE. Lipids versus glucose in inflammation and the pathogenesis of macrovascular disease in diabetes. Curr Diab Rep. 2009;9(1):18-25.
Kennedy A, Martinez K, Chuang C-C, LaPoint K, McIntosh M. Saturated fatty acid-mediated inflammation and insulin resistance in adipose tissue: mechanisms of action and implications. J Nutr. 2009;139(1):1-4.
Taskinen HS, Roytta M. Increased expression of chemokines (MCP-1, MIP-1alpha, RANTES) after peripheral nerve transection. J Peripher Nerv Syst. 2000;5(2):75-81.
Toews AD, Barrett C, Morell P. Monocyte chemoattractant protein 1 is responsible for macrophage recruitment following injury to sciatic nerve. J Neurosci Res. 1998;53(2):260-267.
Stoll G, Jander S, Myers RR. Degeneration and regeneration of the peripheral nervous system: from Augustus Waller's observations to neuroinflammation. J Peripher Nerv Syst. 2002;7(1):13-27.
LeBlanc AC, Poduslo JF. Axonal modulation of myelin gene expression in the peripheral nerve. J Neurosci Res. 1990;26(3):317-326.
Patil S, Chan C. Palmitic and stearic fatty acids induce Alzheimer-like hyperphosphorylation of tau in primary rat cortical neurons. Neurosci Lett. 2005;384(3):288-293.
Patil S, Sheng L, Masserang A, Chan C. Palmitic acid-treated astrocytes induce BACE1 upregulation and accumulation of C-terminal fragment of APP in primary cortical neurons. Neurosci Lett. 2006;406(1-2):55-59.
Yan ZQ. Regulation of TLR4 expression is a tale about tail. Arterioscler Thromb Vasc Biol. 2006;26(12):2582-2584.
Xagorari A, Chlichlia K. Toll-like receptors and viruses: induction of innate antiviral immune responses. Open Microbiol J. 2008;2:49-59.
Shi H, Kokoeva MV, Inouye K, Tzameli I, Yin H, Flier JS. TLR4 links innate immunity and fatty acid-induced insulin resistance. J Clin Invest. 2006;116(11):3015-3025.
Wang Y, Shan X, Chen G, et al. MD-2 as the target of a novel small molecule, L6H21, in the attenuation of LPS-induced inflammatory response and sepsis. Br J Pharmacol. 2015;172(17):4391-4405.
Ii M, Matsunaga N, Hazeki K, et al. A novel cyclohexene derivative, ethyl (6R)-6-[N-(2-Chloro-4-fluorophenyl)sulfamoyl]cyclohex-1-ene-1-carboxylate (TAK-242), selectively inhibits toll-like receptor 4-mediated cytokine production through suppression of intracellular signaling. Mol Pharmacol. 2006;69(4):1288-1295.
Yamada M, Ichikawa T, Ii M, et al. Discovery of novel and potent small-molecule inhibitors of NO and cytokine production as antisepsis agents: synthesis and biological activity of alkyl 6-(N-substituted sulfamoyl)cyclohex-1-ene-1-carboxylate. J Med Chem. 2005;48(23):7457-7467.
Kawamoto T, Ii M, Kitazaki T, Iizawa Y, Kimura H. TAK-242 selectively suppresses Toll-like receptor 4-signaling mediated by the intracellular domain. Eur J Pharmacol. 2008;584(1):40-48.
Matsunaga N, Tsuchimori N, Matsumoto T, Ii M. TAK-242 (resatorvid), a small-molecule inhibitor of Toll-like receptor (TLR) 4 signaling, binds selectively to TLR4 and interferes with interactions between TLR4 and its adaptor molecules. Mol Pharmacol. 2011;79(1):34-41.
Kang JY, Lee JO. Structural biology of the Toll-like receptor family. Annu Rev Biochem. 2011;80:917-941.
Hasegawa K. A new method of measuring functional recovery after crushing the peripheral nerves in unanesthetized and unrestrained rats. Experientia. 1978;34(2):272-273.