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New Usage of Metformin and Salicylic Acid in Anti-Inflammatory
2016-11-15
来源：转载自第三方
15 November 2016
Recently, researches from the University of Glasgow and Bradford University published a paper in 《Science Signaling》, revealed a new inflammatory response-related signaling pathways, and found Two common drugs that can play a role in relieving the inflammatory response——The diabetes drug metformin and salicylic acid.
JAK-STAT, mitogen-activated protein kinase (MAPK) and nuclear factor-kappaB (NF-κB), which are involved in the regulation of cell proliferation and a series of physiological and pathological reaction process, there is a great significance for maintaining the normal physiological function of cells. JAK kinase mediates inflammatory responses in a variety of tissues. When inflammatory cytokines act on receptors on the cell surface, the downstream signaling pathways, JAK-STAT, can activate inflammatory responses to promote cell survival and migration. However, external signals or mutations can lead to abnormal activation of JAK, persistent inflammatory response may causes disease.
In vitro kinase assays revealed that AMPK directly phosphorylated two residues (Ser515 and Ser518) within the Src homology 2 domain of JAK1. Activation of AMPK enhanced the interaction between JAK1 and 14-3-3 proteins in cultured vascular endothelial cells and fibroblasts, an effect that required the presence of Ser515 and Ser518 and was abolished in cells lacking AMPK catalytic subunits. Mutation of Ser515 and Ser518 abolished AMPK-mediated inhibition of JAK-STAT signaling stimulated by either the sIL-6Ra/IL-6 complex or the expression of a constitutively active V658F-mutant JAK1 in human fibrosarcoma cells.
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Clinically used AMPK activators metformin and salicylate enhanced the inhibitory phosphorylation of endogenous JAK1 and inhibited STAT3 phosphorylation in primary vascular endothelial cells. At present, the study is still in the early laboratory stage, the researchers will continue to conduct in-depth study.
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This treatment will be applicable to other cases of abnormal activation of JAK kinase isoforms and their associated diseases. Because AMPK can be activated by a variety of existing diabetes drugs, the future can further study whether these drugs can be used for a variety of inflammation-related diseases.
Related Links: Metformin Hydrochloride
Edited by the Editorial Office of Suzhou Yacoo Science Co., Ltd.
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