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

Int J Mol Sci. 2014 Jul 3;15(7):11817-31. doi: 10.3390/ijms150711817.

Abstract

Background: 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).

Methods: 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.

Results: 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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Asthma / metabolism*
  • Bone Marrow Cells / metabolism*
  • Boron Compounds / pharmacology
  • Cell Degranulation*
  • Cytokines / genetics
  • Cytokines / metabolism*
  • Female
  • Histamine / metabolism
  • Mast Cells / metabolism*
  • Mast Cells / physiology
  • Rats
  • Rats, Sprague-Dawley
  • TRPM Cation Channels / antagonists & inhibitors*
  • TRPM Cation Channels / genetics
  • TRPM Cation Channels / metabolism

Substances

  • Boron Compounds
  • Cytokines
  • TRPM Cation Channels
  • Histamine
  • 2-aminoethoxydiphenyl borate
  • Trpm7 protein, rat