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Updated: Aug 12, 2026
Bone Marrow-derived Macrophage Production
Published on: November 22, 2013
LPS enhances expression of CD204 through the MAPK/ERK pathway in murine bone marrow macrophages
Ryota Hashimoto1, Ryo Kakigi1, Kyoko Nakamura1
1Department of Physiology, Juntendo University Faculty of Medicine, Hongo 2-1-1, Bunkyo-ku, Tokyo 113-8421, Japan.
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 CD36 and 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 CD36 expression, 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 CD36 or 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 CD36 expression.
Conclusions:
These results suggest that LPS may increase Ac-LDL uptake and enhance CD204 expression through MAPK/ERK activation and CD36 expression through an ERK-independent pathway. Since MEK inhibitors block CD204 expression in mouse BM macrophages only under LPS treatment but not under normal conditions, a MEK inhibitor might be a good candidate compound for the treatment of LPS-induced atherosclerosis.
Insights
Lipopolysaccharide (LPS) activates the MAPK/ERK pathway, increasing CD204 and CD36 expression and modified LDL uptake in macrophages. MEK inhibitors block LPS-induced CD204 expression, suggesting therapeutic potential for atherosclerosis.
Area of Science:
- Immunology
- Cardiovascular Biology
- Cellular Signaling
Background:
- Lipopolysaccharide (LPS), a Gram-negative bacterial cell wall component, is linked to atherosclerosis development in periodontal disease.
- LPS increases scavenger receptor expression (CD36, CD204) and modified low-density lipoprotein (LDL) uptake.
- The precise signaling pathways mediating LPS effects on these receptors remain unclear, hindering therapeutic target identification.
Purpose of the Study:
- To elucidate the signaling pathways involved in LPS-induced CD36 and CD204 expression and modified LDL uptake.
- To investigate the role of the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway in these processes.
- To evaluate the potential of MEK inhibitors as therapeutic agents for LPS-induced atherosclerosis.
Main Methods:
- Utilized mouse bone marrow-derived macrophages.
- Investigated the effect of LPS on MAPK/ERK pathway activation.
- Assessed CD36 and CD204 expression levels via Western blotting or similar techniques.
- Quantified acetylated-LDL (Ac-LDL) uptake.
- Employed MEK inhibitors (U0126, PD0325901) to probe pathway involvement.
Main Results:
- LPS activated the MAPK/ERK pathway in macrophages.
- LPS treatment increased both CD36 and CD204 expression and enhanced Ac-LDL uptake.
- MEK inhibitors blocked LPS-induced Ac-LDL uptake and CD204 expression.
- MEK inhibitors did not affect CD36 expression under LPS treatment.
Conclusions:
- LPS enhances Ac-LDL uptake and CD204 expression via MAPK/ERK activation.
- LPS increases CD36 expression through an ERK-independent pathway.
- MEK inhibitors show promise for treating LPS-induced atherosclerosis by targeting CD204 expression.
