LPS enhances expression of CD204 through the MAPK/ERK pathway in murine bone marrow macrophages

Abstract Background and aims Lipopolysaccharide (LPS) is a main component of the Gram-negative bacterial cell wall and is associated with a greater risk of atherosclerosis development in periodontal disease. LPS has been reported to increase both CD36and CD204 expression and enhance the uptake of modified low-density lipoprotein (LDL). However, the signaling pathways by which LPS enhances these expression levels and function have not been fully elucidated, although the clarification of these signaling pathways is important for identifying therapeutic targets for atherosclerosis. Methods and results We have shown here that LPS activated the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway, increased both CD204 and CD36expression, and enhanced the uptake of acetylated-LDL (Ac-LDL) in mouse bone marrow macrophages. The MAPK/ERK kinase ( MEK) inhibitors, U0126 (1 μM) and PD0325901 (10 nM), did not affect the expression of either CD36or CD204 or the uptake of Ac-LDL under normal conditions(no treatment with LPS). In contrast, U0126 (1 μM) and PD0325901 (10 nM) blocked the LPS-induced increase in Ac-LDL uptake and CD204 expression but not CD36expression. Conclusions These results suggest that LPS may increase Ac-LDL uptake and enhance CD204 expression through MAPK/ERK activation and CD36expression through an ERK-independent pathway. Since MEK inhibitorsblock CD204 expression in mouse BM macrophages only under LPS treatment but not under normal conditions, a MEK inhibitormight be a good candidate compound for the treatment of LPS-induced atherosclerosis.