Lysophosphatidic Acid Induces CD14 Protein Expression Via The P38α-mediated In Bone Marrow-Derived Macrophages

Atherosclerosis(AS)is one of the main causes of cardiovascular disease.Its pathological mechanism is mainly due to the accumulation of low-density lipoprotein(LDL)in the sub-endothelial matrix,forming deposits.These deposits cause inflammation in endothelial cells(ECs)and eventually lead to plaque formation.Endothelial cells,macrophages,and smooth muscle cells are the main cell types that contribute to the development of atherosclerosis.CD14(Cluster of differentiation antigen 14)is a membrane glycoprotein widely expressed on the surface of macrophages,dendritic cells,and other immune cells.In the progression of atherosclerosis,CD14 promotes macrophage uptake of oxidized low-density lipoprotein(ox-LDL)and foam cell formation.Therefore,exploring the regulatory mechanism of CD14 expression in macrophages can help to better understand the molecular mechanisms of atherosclerosis.Lysophosphatidic acid(LPA)is an active phospholipid.LPA can stimulate various signaling pathways in cells by binding to specific LPA receptors,thereby affecting biological processes such as cell proliferation,migration,apoptosis,and inflammatory response.The action of LPA can activate and chemotaxis various immune and inflammation-related cells.To investigate the molecular mechanism of LPA on CD14 expression in macrophages,we used Western blot to detect changes in CD14 protein expression induced by LPA.It was found that LPA-induced CD14 protein expression in macrophages has time and concentration dependence.To further investigate the molecular mechanism of LPA-induced CD14 expression,we used WB to detect the expression levels of MAPK-related proteins and found that LPA can significantly induce phosphorylation of JNK and p38 and dephosphorylation of ERK,and it has time dependence.LPA has an impact on the basal levels of the three MAP kinases,suggesting that these three MAP kinases may all participate in LPA-mediated CD14 expression in bone marrow macrophages(BMMs).Next,we treated macrophages with ERK,JNK,and p38 inhibitors,and found that the p38 inhibitor can effectively inhibit LPA-induced CD14 expression.Finally,through si RNA experiments,we knocked down the expression of the p38α subtype in macrophages and found that it can partially inhibit LPA-induced CD14 expression.This indicates that LPA induces CD14 expression through the p38α pathway.This study proposes the signaling pathway and regulatory mechanism of LPAinduced CD14 expression in bone marrow macrophages,and identifies the important regulatory role of the p38α subtype.This study provides new ideas for the treatment of cardiovascular inflammatory diseases.