Functional Interleukin-17 Receptor A is Expressed in Central Nervous System Glia and Upregulated in Experimental Autoimmune Encephalomyelitis
Data(s) |
28/04/2009
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Resumo |
Background: Interleukin-17A (IL-17A) is the founding member of a novel family of inflammatory cytokines that plays a critical role in the pathogenesis of many autoimmune diseases, including multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). IL-17A signals through its receptor, IL-17RA, which is expressed in many peripheral tissues; however, expression of IL-17RA in the central nervous system (CNS) and its role in CNS inflammation are not well understood. Methods: EAE was induced in C57Bl/6 mice by immunization with myelin oligodendroglial glycoprotein. IL-17RA expression in the CNS was compared between control and EAE mice using RT-PCR, in situ hybridization, and immunohistochemistry. Cell-type specific expression was examined in isolated astrocytic and microglial cell cultures. Cytokine and chemokine production was measured in IL-17A treated cultures to evaluate the functional status of IL-17RA. Results: Here we report increased IL-17RA expression in the CNS of mice with EAE, and constitutive expression of functional IL-17RA in mouse CNS tissue. Specifically, astrocytes and microglia express IL-17RA in vitro, and IL-17A treatment induces biological responses in these cells, including significant upregulation of MCP-1, MCP-5, MIP-2 and KC chemokine secretion. Exogenous IL-17A does not significantly alter the expression of IL-17RA in glial cells, suggesting that upregulation of chemokines by glial cells is due to IL-17A signaling through constitutively expressed IL-17RA. Conclusion: IL-17RA expression is significantly increased in the CNS of mice with EAE compared to healthy mice, suggesting that IL-17RA signaling in glial cells can play an important role in autoimmune inflammation of the CNS and may be a potential pathway to target for therapeutic interventions. © 2009 Sarma et al; licensee BioMed Central Ltd. |
Identificador |
http://dx.doi.org/10.1186/1742-2094-6-14 http://www.scopus.com/inward/record.url?scp=67449155295&partnerID=8YFLogxK |
Idioma(s) |
eng |
Direitos |
info:eu-repo/semantics/restrictedAccess |
Fonte |
Sarma , J D , Ciric , B , Marek , R , Sadhukhan , S , Caruso , M L , Shafagh , J , Fitzgerald , D C , Shindler , K S & Rostami , A 2009 , ' Functional Interleukin-17 Receptor A is Expressed in Central Nervous System Glia and Upregulated in Experimental Autoimmune Encephalomyelitis ' Journal of Neuroinflammation , vol 6 , 14 . DOI: 10.1186/1742-2094-6-14 |
Palavras-Chave | #/dk/atira/pure/subjectarea/asjc/2400/2403 #Immunology #/dk/atira/pure/subjectarea/asjc/2800 #Neuroscience(all) #/dk/atira/pure/subjectarea/asjc/2800/2804 #Cellular and Molecular Neuroscience #/dk/atira/pure/subjectarea/asjc/2800/2808 #Neurology |
Tipo |
article |