Lysophosphatidic Acid Promotes Expression and Activation of Matrix Metalloproteinase 9 (MMP9) in THP-1 Cells via Toll-Like Receptor 4/Nuclear Factor-κB (TLR4/NF-κB) Signaling Pathway

Medical Science Monitor : International Medical Journal of Experimental and Clinical Research
Zhibin ZhouGang Lei

Abstract

BACKGROUND Lysophosphatidic acid (LPA) is an active compound of oxidized low-density lipoprotein that serves as an endogenous TLR4 ligand. Ligand activation of TLR4 activates nuclear factor-kappaB (NF-κB) and the transcription of NF-κB-regulated inflammatory cytokines, which are involved in the development of atherosclerosis. MMP9 is a member of the MMP family and can affect plaque stability. However, the mechanism responsible for the effect of LPA on the expression and activation of MMP9 has not been fully elucidated. In the present study we examined the effect of LPA on MMP9 expression and activity in THP-1 cells and the involvement of Toll-like receptor 4/nuclear factor-κB (TLR4/NF-κB) signaling pathway in this effect. MATERIAL AND METHODS Human THP-1 cells were treated with 0-10 μM LPA for 4 h, or treated with 1 μM LPA for 0-8 h, and were then transfected with TLR4-specific siRNA or treated with 20 μg/ml cafestol acid phenethyl ester (CAPE, an NF-κB inhibitor). MMP9 mRNA and protein levels were measured by quantitative RT-PCR and Western blot analysis, respectively, and MMP9 activity was measured by zymography. RESULTS LPA upregulated MMP9 mRNA and protein levels and MMP9 activity in THP-1 cells in both concentration- and t...Continue Reading

Citations

Mar 9, 2019·International Journal of Molecular Sciences·Shi-Hui LawLiang-Yin Ke
Jul 1, 2020·International Journal of Molecular Sciences·Eva Knuplez, Gunther Marsche
Jun 23, 2020·ACS Pharmacology & Translational Science·Ying ZhouDanielle Kamato

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