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.
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Abbreviations
- TRPC:
-
Transient receptor potential canonical
- MS:
-
Multiple sclerosis
- EAE:
-
Experimental autoimmune encephalomyelitis
- CNS:
-
Central nervous system
- DMEM:
-
Dulbecco’s modified Eagle’s medium
- FBS:
-
Fetal bovine serum
- PVDF:
-
Polyvinylidene difluoride
- TBST:
-
Tris-buffered saline with Tween-20
- GFAP:
-
Glial fibrillary acidic protein
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Acknowledgments
This work was supported by grants from the National Natural Science Foundation of China (Nos. 81322048, 81473190), Award for Jiangsu Specially Appointed Professor and the Major State Basic Research Development Program of China (973 Program) (2013CB733800, 2013CB733803). Award for the Open Fund of the State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, China (Grant no. KF-GN-201401) and Jiangsu Planned Projects for Postdoctoral Research Funds (Grant no. 1402152C).
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Zhang, Y., Huang, R., Zhang, Y. et al. IL-17 induces MIP-1α expression in primary mouse astrocytes via TRPC channel. Inflammopharmacol 24, 33–42 (2016). https://doi.org/10.1007/s10787-015-0256-x
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DOI: https://doi.org/10.1007/s10787-015-0256-x