TRPM channels as potential therapeutic targets against pro-inflammatory diseases

Cell Calcium. 2017 Nov:67:105-115. doi: 10.1016/j.ceca.2017.05.002. Epub 2017 May 3.

Abstract

The immune system protects our body against foreign pathogens. However, if it overshoots or turns against itself, pro-inflammatory diseases, such as rheumatoid arthritis, inflammatory bowel disease, or diabetes develop. Ions, the most basic signaling molecules, shape intracellular signaling cascades resulting in immune cell activation and subsequent immune responses. Mutations in ion channels required for calcium signaling result in human immunodeficiencies and highlight those ion channels as valued targets for therapies against pro-inflammatory diseases. Signaling pathways regulated by melastatin-like transient receptor potential (TRPM) cation channels also play crucial roles in calcium signaling and leukocyte physiology, affecting phagocytosis, degranulation, chemokine and cytokine expression, chemotaxis and invasion, as well as lymphocyte development and proliferation. Therefore, this review discusses their regulation, possible interactions and whether they can be exploited as targets for therapeutic approaches to pro-inflammatory diseases.

Keywords: Calcium; Immune cells; Immunity; Magnesium; Pro-inflammatory diseases; TRPM channel; signaling; α-Kinase.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity / drug effects
  • Animals
  • Anti-Inflammatory Agents / therapeutic use*
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / genetics
  • Arthritis, Rheumatoid / immunology
  • Arthritis, Rheumatoid / pathology
  • Calcium / immunology
  • Calcium / metabolism*
  • Calcium Signaling
  • Diabetes Mellitus / drug therapy*
  • Diabetes Mellitus / genetics
  • Diabetes Mellitus / immunology
  • Diabetes Mellitus / pathology
  • Gene Expression Regulation
  • Humans
  • Immunity, Innate / drug effects
  • Inflammatory Bowel Diseases / drug therapy*
  • Inflammatory Bowel Diseases / genetics
  • Inflammatory Bowel Diseases / immunology
  • Inflammatory Bowel Diseases / pathology
  • Lymphocytes / drug effects
  • Lymphocytes / immunology
  • Lymphocytes / pathology
  • Magnesium / immunology
  • Magnesium / metabolism
  • Mast Cells / drug effects
  • Mast Cells / immunology
  • Mast Cells / pathology
  • Phagocytes / drug effects
  • Phagocytes / immunology
  • Phagocytes / pathology
  • Protein Isoforms / antagonists & inhibitors
  • Protein Isoforms / genetics
  • Protein Isoforms / immunology
  • TRPM Cation Channels / antagonists & inhibitors
  • TRPM Cation Channels / genetics*
  • TRPM Cation Channels / immunology

Substances

  • Anti-Inflammatory Agents
  • Protein Isoforms
  • TRPM Cation Channels
  • Magnesium
  • Calcium