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Published on: September 14, 2021

Role of JAK/STAT pathway in IL-6-induced activation of vascular smooth muscle cells

Susumu Watanabe1, Wei Mu, Andrew Kahn

  • 1Baylor College of Medicine, Houston, Tex., USA. susumuw@showa-university-fujigaoka.gr.jp

American Journal of Nephrology
|July 17, 2004
PubMed
Abstract

Insights

Interleukin-6 (IL-6) stimulates vascular smooth muscle cell proliferation and MCP-1 release via the JAK/STAT pathway. This pathway partially mediates IL-6 effects, suggesting a role in vascular disease development.

Area of Science:

  • Vascular Biology
  • Cell Signaling
  • Immunology

Background:

  • Interleukin-6 (IL-6) is implicated in vascular disease and atherosclerosis.
  • IL-6 directly affects vascular smooth muscle cells (VSMC), inducing proliferation and monocyte chemoattractant protein-1 (MCP-1) release.
  • The janus-activated kinase (JAK)/signal and transducers and activators of transcription (STAT) pathway is a potential mediator of IL-6 effects.

Purpose of the Study:

  • To investigate the role of the JAK/STAT signaling pathway in mediating IL-6-induced responses in VSMC.
  • To determine if JAK/STAT pathway activation is necessary for IL-6-stimulated VSMC proliferation and MCP-1 production.

Main Methods:

  • Rat VSMC were treated with IL-6.
  • JAK 2 inhibitor (AG490) was used to block JAK/STAT signaling.
  • STAT 3 activation (Western blot), MCP-1 production (ELISA), and DNA synthesis ((3)H-thymidine incorporation) were measured.

Main Results:

  • IL-6 induced rapid, dose- and time-dependent STAT 3 phosphorylation.
  • IL-6 stimulated MCP-1 protein production and DNA synthesis.
  • AG490 partially inhibited STAT 3 activation and MCP-1 production, but nearly completely inhibited DNA synthesis.

Conclusions:

  • The JAK/STAT pathway partially mediates IL-6-induced MCP-1 production and DNA synthesis in VSMC.
  • These findings highlight the JAK/STAT pathway's role in the pathogenesis of vascular disease and atherosclerosis.

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