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- Title
Role of JAK/STAT pathway in IL-6-induced activation of vascular smooth muscle cells.
- Authors
Watanabe, Susumu; Mu, Wei; Kahn, Andrew; Jing, Naijie; Li, Jin H.; Lan, Hui Y.; Nakagawa, Takahiko; Ohashi, Ryuji; Johnson, Richard J.
- Abstract
<bold>Background/aims: </bold>IL-6, an inducer of the acute-phase response, is linked with the development of vascular disease and atherosclerosis. One mechanism likely involves direct effects of IL-6 on vascular smooth muscle cells (VSMC), for IL-6 can induce VSMC proliferation and the release of monocyte chemoattractant protein-1 (MCP-1). We hypothesized that this stimulation occurs via the JAK (janus-activated kinase)/STAT (signal and transducers and activators of transcription) signaling pathway.<bold>Methods: </bold>Rat VSMC were stimulated with IL-6 in the presence or absence of a JAK 2 inhibitor, and the activation of STAT 3 (by Western), MCP-1 (by ELISA) and DNA synthesis (by (3)H-thymidine incorporation) was determined.<bold>Results: </bold>IL-6 rapidly induced phosphorylation of STAT 3 in a dose- and time-dependent manner with a peak expression at 30 min. IL-6 also stimulated MCP-1 protein production and DNA synthesis dose dependently. 50 microM of AG490, a specific JAK 2 inhibitor, partially inhibited STAT 3 activation and MCP-1 production, with near complete inhibition of DNA synthesis.<bold>Conclusion: </bold>The JAK/STAT pathway partially mediates IL-6-induced MCP-1 production and DNA synthesis in rat VSMC. These studies implicate a role of the JAK/STAT pathway in the development of vascular disease and atherosclerosis.
- Publication
American Journal of Nephrology, 2004, Vol 24, Issue 4, p387
- ISSN
0250-8095
- Publication type
journal article
- DOI
10.1159/000079706