Inhibition of TRPM7 channels reduces degranulation and release of cytokines in rat bone marrow-derived mast cells.

Linjie Huang, Ngai-Mui Ng, Ming Chen, Xiaoling Lin, Tiantian Tang, Huihua Cheng, Cheng Yang, Shanping Jiang

Index: Int. J. Mol. Sci. 15(7) , 11817-31, (2014)

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Abstract

mast cells play an important role in airway inflammation in asthma. The transient receptor potential melastatin-like 7 (TRPM7) channel is expressed in primary human lung mast cells and plays a critical role for cell survival. This study aimed to investigate the role of TRPM7 on degranulation and release of cytokines in rat bone marrow-derived mast cells (BMMCs).the expression levels of TRPM7 were observed by immunocytochemistry and RT-PCR between normal and asthmatic rat BMMCs. TRPM7-specific shRNA and 2-aminoethoxydiphenyl borate (2-APB) and specific shTRPM7 were used to inhibit the function of TRPM7. Degranulation levels were analyzed by beta-hexosaminidase assay. Histamine, TNF-α, IL-6 and IL-13 levels were measured by ELISA.the expression of TRPM7 was significantly higher in asthmatic rat BMMCs than in the normal control group. After application of 2-APB and down-regulation of TRPM7, the beta-hexosaminidase activity and secretion of histamine, IL-6, IL-13 and TNF-α were significantly decreased in the asthmatic group compared to the control group.this study indicates that TRPM7 channels may be involved in the process of degranulation and release of cytokines in rat bone marrow-derived mast cells.