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Regulation of TRPM7 Function by IL-6 through the JAK2-STAT3 Signaling Pathway

Aifen Liu1,2, Fengbo Zhao1,2, Jing Wang1

  • 1Department of Neurobiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, P.R. China.

Plos One
|March 25, 2016
PubMed
Abstract

Insights

Interleukin-6 (IL-6) inhibits the TRPM7 channel, a key player in calcium influx and cell death. This regulation occurs through the JAK2-STAT3 signaling pathway, offering new insights into TRPM7 channel function.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Cell Physiology

Background:

  • The transient receptor potential melastatin 7 (TRPM7) channel regulates calcium influx and cell death.
  • The functional regulation of TRPM7 channels by endogenous molecules remains largely unknown.
  • Interleukin-6 (IL-6), a pro-inflammatory cytokine, influences calcium influx in cerebral ischemia, but its role in TRPM7 channel regulation is unclear.

Purpose of the Study:

  • To investigate the interaction between IL-6 and TRPM7 channels.
  • To elucidate the underlying mechanisms of IL-6's regulation of TRPM7 channel function.

Main Methods:

  • Whole-cell patch-clamp electrophysiology in primary cortical neurons.
  • TRPM7-overexpressing HEK293 cells to confirm IL-6/sIL-6R effects.
  • Pharmacological inhibition of specific signaling pathways (JAK2-STAT3, PI3K, ERK1/2, PLC).

Main Results:

  • IL-6 and IL-6/soluble IL-6 receptor (sIL-6R) dose-dependently inhibited inward TRPM7 currents in both neurons and HEK293 cells.
  • Regulation was independent of extracellular calcium and the TRPM7 α-kinase domain under Mg2+-free conditions.
  • The inhibitory effect of IL-6 was specifically blocked by JAK2-STAT3 pathway inhibitors.

Conclusions:

  • IL-6 inhibits TRPM7 channel activity.
  • This inhibition is mediated by the Janus kinase 2 (JAK2)-signal transducer and activator of transcription 3 (STAT3) signaling pathway.
  • Findings reveal a novel regulatory mechanism for TRPM7 channels by IL-6.

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