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The Stimulation of CD147 Induces MMP-9 Expression through ERK and NF-kappaB in Macrophages: Implication for Atherosclerosis.

Kim JY, Kim WJ, Kim H, Suk K, Lee WH - Immune Netw (2009)

Bottom Line: Recent observations showing the expression of CD147 in leukocytes indicate that this molecule may have roles in inflammation.Staining of both CD147 and CypA was detected in endothelial cell layers facing the lumen and macrophage-rich areas.These results suggest that CD147 mediates the inflammatory activation of macrophages that leads to the induction of MMP-9 expression, which could play a role in the pathogenesis of inflammatory diseases such as atherosclerosis.

View Article: PubMed Central - PubMed

Affiliation: The School of Life Sciences and Biotechnology, Kyungpook National University, Daegu 702-701, Korea.

ABSTRACT

Background: CD147, as a cellular receptor for cyclophilin A (CypA), is a multifunctional protein involved in tumor invasion, inflammation, tissue remodeling, neural function, and reproduction. Recent observations showing the expression of CD147 in leukocytes indicate that this molecule may have roles in inflammation.

Methods: In order to investigate the role of CD147 and its ligand in the pathogenesis of atherosclerosis, human atherosclerotic plaques were analyzed for the expression pattern of CD147 and CypA. The cellular responses and signaling molecules activated by the stimulation of CD147 were then investigated in the human macrophage cell line, THP-1, which expresses high basal level of CD147 on the cell surface.

Results: Staining of both CD147 and CypA was detected in endothelial cell layers facing the lumen and macrophage-rich areas. Stimulation of CD147 with its specific monoclonal antibody induced the expression of matrix metalloproteinase (MMP)-9 in THP-1 cells and it was suppressed by inhibitors of both ERK and NF-kappaB. Accordingly, the stimulation of CD147 was observed to induce phosphorylation of ERK, phosphorylation-associated degradation of IkappaB, and nuclear translocation of NF-kappaB p65 and p50 subunits.

Conclusion: These results suggest that CD147 mediates the inflammatory activation of macrophages that leads to the induction of MMP-9 expression, which could play a role in the pathogenesis of inflammatory diseases such as atherosclerosis.

No MeSH data available.


Related in: MedlinePlus

Endothelial cells and macrophages express CD147 and CypA in atherosclerotic plaques. Human carotid atherosclerotic plaques were sequentially sectioned and stained against CD68 (a macrophage marker), vWF (an endothelial cell marker), CD147, CypA. Mouse IgG (mIgG) was used for the staining as a negative control. Upper panel shows the plaques area facing the vessel lumen (L). Lower panel shows the shoulder area of a plaque which have macrophages and smooth muscle cells (SM). Note the low level staining of CypA in areas rich in SMCs.
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Figure 1: Endothelial cells and macrophages express CD147 and CypA in atherosclerotic plaques. Human carotid atherosclerotic plaques were sequentially sectioned and stained against CD68 (a macrophage marker), vWF (an endothelial cell marker), CD147, CypA. Mouse IgG (mIgG) was used for the staining as a negative control. Upper panel shows the plaques area facing the vessel lumen (L). Lower panel shows the shoulder area of a plaque which have macrophages and smooth muscle cells (SM). Note the low level staining of CypA in areas rich in SMCs.

Mentions: In order to analyze the role of CD147 and its ligand (CypA) in atherogenic processes, human carotid atherosclerotic plaques were analyzed using immunohistochemical analysis (Fig. 1). The innermost layer of atherosclerotic plaque facing the lumen was lined with endothelial cells which are specifically stained with mAb against the von Willebrand factor (vWF). vWF is a multimeric glycoprotein essential for thrombus formation and the plasma level of it has been shown to be elevated in patients with atherosclerosis (29,30). Since the expression of vWF is restricted to platelets and endothelial cells, its presence has been used as a endothelial cell marker in a number of studies employing immunohistochemistry (31,32). Macrophages, stained with anti-CD68 mAb, were found in large numbers at the shoulder region of plaques in between thick layers of SMCs (Fig. 1, lower panel). CD147 expression was detected in the innermost layers facing the lumen, which corresponds to endothelial cells (Fig. 1, upper panel), and in the area corresponding to macrophage-rich regions in the shoulder region (Fig. 1, lower panel). The expression of CD147 in SMCs was not detected. Interestingly, the expression pattern of CypA, the ligand for CD147, was similar to that of CD147: both endothelial cell- and macrophage-rich areas.


The Stimulation of CD147 Induces MMP-9 Expression through ERK and NF-kappaB in Macrophages: Implication for Atherosclerosis.

Kim JY, Kim WJ, Kim H, Suk K, Lee WH - Immune Netw (2009)

Endothelial cells and macrophages express CD147 and CypA in atherosclerotic plaques. Human carotid atherosclerotic plaques were sequentially sectioned and stained against CD68 (a macrophage marker), vWF (an endothelial cell marker), CD147, CypA. Mouse IgG (mIgG) was used for the staining as a negative control. Upper panel shows the plaques area facing the vessel lumen (L). Lower panel shows the shoulder area of a plaque which have macrophages and smooth muscle cells (SM). Note the low level staining of CypA in areas rich in SMCs.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2803300&req=5

Figure 1: Endothelial cells and macrophages express CD147 and CypA in atherosclerotic plaques. Human carotid atherosclerotic plaques were sequentially sectioned and stained against CD68 (a macrophage marker), vWF (an endothelial cell marker), CD147, CypA. Mouse IgG (mIgG) was used for the staining as a negative control. Upper panel shows the plaques area facing the vessel lumen (L). Lower panel shows the shoulder area of a plaque which have macrophages and smooth muscle cells (SM). Note the low level staining of CypA in areas rich in SMCs.
Mentions: In order to analyze the role of CD147 and its ligand (CypA) in atherogenic processes, human carotid atherosclerotic plaques were analyzed using immunohistochemical analysis (Fig. 1). The innermost layer of atherosclerotic plaque facing the lumen was lined with endothelial cells which are specifically stained with mAb against the von Willebrand factor (vWF). vWF is a multimeric glycoprotein essential for thrombus formation and the plasma level of it has been shown to be elevated in patients with atherosclerosis (29,30). Since the expression of vWF is restricted to platelets and endothelial cells, its presence has been used as a endothelial cell marker in a number of studies employing immunohistochemistry (31,32). Macrophages, stained with anti-CD68 mAb, were found in large numbers at the shoulder region of plaques in between thick layers of SMCs (Fig. 1, lower panel). CD147 expression was detected in the innermost layers facing the lumen, which corresponds to endothelial cells (Fig. 1, upper panel), and in the area corresponding to macrophage-rich regions in the shoulder region (Fig. 1, lower panel). The expression of CD147 in SMCs was not detected. Interestingly, the expression pattern of CypA, the ligand for CD147, was similar to that of CD147: both endothelial cell- and macrophage-rich areas.

Bottom Line: Recent observations showing the expression of CD147 in leukocytes indicate that this molecule may have roles in inflammation.Staining of both CD147 and CypA was detected in endothelial cell layers facing the lumen and macrophage-rich areas.These results suggest that CD147 mediates the inflammatory activation of macrophages that leads to the induction of MMP-9 expression, which could play a role in the pathogenesis of inflammatory diseases such as atherosclerosis.

View Article: PubMed Central - PubMed

Affiliation: The School of Life Sciences and Biotechnology, Kyungpook National University, Daegu 702-701, Korea.

ABSTRACT

Background: CD147, as a cellular receptor for cyclophilin A (CypA), is a multifunctional protein involved in tumor invasion, inflammation, tissue remodeling, neural function, and reproduction. Recent observations showing the expression of CD147 in leukocytes indicate that this molecule may have roles in inflammation.

Methods: In order to investigate the role of CD147 and its ligand in the pathogenesis of atherosclerosis, human atherosclerotic plaques were analyzed for the expression pattern of CD147 and CypA. The cellular responses and signaling molecules activated by the stimulation of CD147 were then investigated in the human macrophage cell line, THP-1, which expresses high basal level of CD147 on the cell surface.

Results: Staining of both CD147 and CypA was detected in endothelial cell layers facing the lumen and macrophage-rich areas. Stimulation of CD147 with its specific monoclonal antibody induced the expression of matrix metalloproteinase (MMP)-9 in THP-1 cells and it was suppressed by inhibitors of both ERK and NF-kappaB. Accordingly, the stimulation of CD147 was observed to induce phosphorylation of ERK, phosphorylation-associated degradation of IkappaB, and nuclear translocation of NF-kappaB p65 and p50 subunits.

Conclusion: These results suggest that CD147 mediates the inflammatory activation of macrophages that leads to the induction of MMP-9 expression, which could play a role in the pathogenesis of inflammatory diseases such as atherosclerosis.

No MeSH data available.


Related in: MedlinePlus