title: IL-17 induces MIP-1α expression in primary mouse astrocytes via TRPC channel.
abstract: Our previous study demonstrated IL-17-mediated induction of MIP-1α through its binding to the cognate IL-17RA and MIP-1α was involved in astrocyte activation. Transient receptor potential canonical (TRPC) channel was involved in astrocyte activation, however, whether TRPC channel regulates MIP-1α expression in the context of multiple sclerosis (MS) remains largely unknown. In this study we identify the essential role of TRPC channel in IL-17-mediated MIP-1α expression and astrocyte activation. Moreover, treatment of astrocytes with IL-17 activated MAPKs and PI3K/Akt signaling pathways with downstream NF-κB pathways. Interestingly, the TRPC blocker-SKF96365 (10 μM) and Norgestimate (10 μM) significantly inhibited the increased expression of MIP-1α via suppression of IL-17-mediated ERK, p38 and JNK MAPKs and PI3K/Akt pathway activation, thereby underscoring the role of TRPC channel in this process. Together these data underpin the role of TRPC channel as a novel target that regulates MIP-1α expression and cell activation-mediated by IL-17 with implications for therapeutic intervention for reversal of neuroinflammation inflicted by IL-17. Understanding the regulation of MIP-1α expression may provide insights into the development of potential therapeutic targets for neuroinflammation associated with MS.
authors.affiliation: Department of Pharmacology, School of Medicine, Southeast University, Nanjing, 210009, Jiangsu, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, School of Medicine, Southeast University, Nanjing, 210009, Jiangsu, China.
authors.forename: Rongrong
authors.initials: R
authors.lastname: Huang
authors.affiliation: Department of Pharmacology, School of Medicine, Southeast University, Nanjing, 210009, Jiangsu, China.
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, School of Medicine, Southeast University, Nanjing, 210009, Jiangsu, China.|State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Yi
authors.affiliation: Department of Pharmacology, School of Medicine, Southeast University, Nanjing, 210009, Jiangsu, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Bai
authors.affiliation: Department of Physiology, Medical School of Southeast University, Nanjing, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Chao
authors.affiliation: Department of Pharmacology, School of Medicine, Southeast University, Nanjing, 210009, Jiangsu, China. yaohh@seu.edu.cn.|Institute of Life Sciences, Key Laboratory of Developmental Genes and Human Disease, Southeast University, Nanjing, China. yaohh@seu.edu.cn.
authors.forename: Honghong
authors.initials: H
authors.lastname: Yao
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D054405:Chemokine CCL3 / Q000235:genetics*; D020381:Interleukin-17 / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009103:Multiple Sclerosis / Q000503:physiopathology; D016328:NF-kappa B / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D050051:Transient Receptor Potential Channels / Q000378:metabolism*
chemical_list: D054405:Chemokine CCL3; D020381:Interleukin-17; D016328:NF-kappa B; D050051:Transient Receptor Potential Channels; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt
keywords: Astrocytes; IL-17; MIP-1α, CCL3; TRPC