The JAK2-Akt-glycogen synthase kinase-3β signaling pathway is involved in toll-like receptor 2-induced monocyte chemoattractant protein-1 regulation

Park,Dae-Weon; Lee,Hyung-Kyoung; Jeong,Tae-Whal; Kim,Jin-Sik; Bae,Yoe-Sik; Chin,Byung-Rho; Baek,Suk-Hwan

doi:10.3892/mmr.2012.741

The JAK2-Akt-glycogen synthase kinase-3β signaling pathway is involved in toll-like receptor 2-induced monocyte chemoattractant protein-1 regulation

Authors:
- Dae-Weon Park
- Hyung-Kyoung Lee
- Tae-Whal Jeong
- Jin-Sik Kim
- Yoe-Sik Bae
- Byung-Rho Chin
- Suk-Hwan Baek
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Affiliations: Department of Biochemistry and Molecular Biology, Aging-associated Vascular Disease Research Center, 210 Main Building, College of Medicine, Yeungnam University, Daegu 705-802, Republic of Korea, Department of Dentistry, College of Medicine, Yeungnam University, Daegu 705-802, Republic of Korea, Department of Biological Science, Sungkyunkwan University, Suwon 440-746, Republic of Korea, Department of Biochemistry and Molecular Biology, Aging-associated Vascular Disease Research Center, 210 Main Building, College of Medicine, Yeungnam University, Daegu 705-802, Republic of Korea
Published online on: January 3, 2012 https://doi.org/10.3892/mmr.2012.741
Pages: 1063-1067

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Abstract

Monocyte chemoattractant protein-1 (MCP-1) is an essential cytokine for the migration of monocytes into vessels, and is also involved in the pathogenesis of atherosclerosis. In this study, we investigated the importance of janus kinase 2 (JAK2) and the function of the Akt and glycogen synthase kinase-3β (GSK3β) pathway in toll-like receptor (TLR2)-mediated MCP-1 expression. The TLR2 agonist, Pam3CSK4, induced MCP-1 expression in the Raw264.7 cell line. The induction of MCP-1 was seen in the bone marrow-derived macrophages of wild-type mice but not in TLR2 knockout mice. The TLR2-mediated MCP-1 induction was myeloid differentiation primary response gene 88 (MyD88)-independent. By contrast, the inactivation of JAK2 attenuated TLR2-mediated MCP-1 expression. The JAK inhibitor suppressed the phosphorylation of GSK3β as well as Akt by Pam3CSK4 stimulation. While the inactivation of Akt by LY294002 suppressed TLR2-mediated MCP-1 induction, the inactivation of GSK3β by LiCl potentiated TLR2-mediated MCP-1 induction. Furthermore, Akt inhibitor suppressed TLR2-mediated phosphorylation of GSK3β. Taken together, these results suggest that a MyD88-independent pathway exists in TLR2 signaling; the JAK2-Akt-GSK3β pathway is a novel MyD88-independent pathway for MCP-1 induction.

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