TRPM5 Negatively Regulates Calcium-Dependent Responses in Lipopolysaccharide-Stimulated B Lymphocytes

Cell Rep. 2020 Jun 9;31(10):107755. doi: 10.1016/j.celrep.2020.107755.

Abstract

B cells produce high amounts of cytokines and immunoglobulins in response to lipopolysaccharide (LPS) stimulation. Calcium signaling cascades are critically involved in cytokine production of T cells, and the cytosolic calcium concentration is regulated by calcium-activated monovalent cation channels (CAMs). Calcium signaling is also implicated in B cell activation; however, its involvement in the cytokine production of LPS-stimulated B cells remains less well characterized. Here, we show that the transient receptor potential melastatin 5 channel (TRPM5), which is one of the CAMs, negatively modulates calcium signaling, thereby regulating LPS-induced proliferative and inflammatory responses by B cells. LPS-stimulated B cells of Trpm5-deficient mice exhibit an increased cytosolic calcium concentration, leading to enhanced proliferation and the production of the inflammatory cytokines interleukin-6 and CXCL10. Furthermore, Trpm5-deficient mice show an exacerbation of endotoxic shock with high mortality. Our findings demonstrate the importance of TRPM5-dependent regulatory mechanisms in LPS-induced calcium signaling of splenic B cells.

Keywords: B lymphocytes; Ca(2+) signaling; IL-6; TRPM5; endotoxic shock.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / metabolism*
  • Calcium / metabolism*
  • HEK293 Cells
  • Humans
  • Lipopolysaccharides / pharmacology
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred C57BL
  • RAW 264.7 Cells
  • Signal Transduction
  • TRPM Cation Channels / metabolism*

Substances

  • Lipopolysaccharides
  • TRPM Cation Channels
  • TRPM5 protein, human
  • Trpm5 protein, mouse
  • Calcium