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Cholinergic agonists regulate JAK2/STAT3 signaling to suppress endothelial cell activation
Prodyot K Chatterjee1, Yousef Al-Abed, Barbara Sherry
1The Center for Immunology and Inflammation, The Feinstein Institute for Medical Research, Manhasset, New York, USA.
American Journal of Physiology. Cell Physiology
|September 11, 2009
Summary
Cholinergic agonists, like nicotine, reduce inflammation by inhibiting IL-6 signaling in endothelial cells via the JAK2/STAT3 pathway. This mechanism offers potential therapeutic strategies for inflammatory conditions.
Area of Science:
- Immunology
- Cell Biology
- Pharmacology
Background:
- The cholinergic anti-inflammatory pathway regulates inflammation by inhibiting cytokine production.
- Cholinergic stimulation is known to suppress endothelial cell activation and leukocyte recruitment.
Purpose of the Study:
- To investigate the mechanisms by which cholinergic agonists regulate endothelial cell activation.
- Specifically, to examine the effects of cholinergic agonists on IL-6-mediated endothelial cell activation via the JAK2/STAT3 signaling pathway.
Main Methods:
- Treatment of human umbilical vein endothelial cells (HUVECs) and microvascular endothelial cells (MVECs) with cholinergic agonists (nicotine, GTS-21).
- Assessed IL-6-mediated production of monocyte chemoattractant protein-1 (MCP-1) and ICAM-1 expression.
- Analyzed JAK2/STAT3 pathway activation, including STAT3 phosphorylation and DNA binding, and SOCS3 levels.
Main Results:
- Cholinergic agonists significantly reduced IL-6-mediated MCP-1 production and ICAM-1 expression in endothelial cells.
- Treatment decreased STAT3 phosphorylation and DNA binding, indicating inhibition of the JAK2/STAT3 pathway.
- Cholinergic agonists also reduced JAK2 phosphorylation and levels of SOCS3, a key regulator of IL-6 signaling.
Conclusions:
- Cholinergic agonists suppress IL-6-mediated endothelial cell activation by inhibiting the JAK2/STAT3 signaling pathway.
- These findings highlight the therapeutic potential of cholinergic agonists for inflammatory conditions driven by IL-6.
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