Cysteinyl Leukotrienes Induce Monocyte Chemoattractant Protein-1 in Human Monocyte/Macrophages via Mitogen-Activated Protein Kinase and Nuclear Factor-κB Pathways

2009 ◽  
Vol 149 (3) ◽  
pp. 275-282 ◽  
Author(s):  
Kunio Hashimoto ◽  
Takashi Ichiyama ◽  
Masanari Hasegawa ◽  
Shunji Hasegawa ◽  
Tomoyo Matsubara ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Human Monocyte ◽  
Nuclear Factor Κb ◽  
Mitogen Activated Protein Kinase ◽  
Nuclear Factor ◽  
Cysteinyl Leukotrienes ◽  
Monocyte Chemoattractant Protein 1 ◽  
Monocyte Chemoattractant ◽  
Monocyte Chemoattractant Protein ◽  
Mitogen Activated Protein

scholarly journals Hypoxia/reoxygenation induction of monocyte chemoattractant protein-1 in melanoma cells: involvement of nuclear factor-κB, stimulatory protein-1 transcription factors and mitogen-activated protein kinase pathways

2002 ◽  
Vol 366 (1) ◽  
pp. 299-306 ◽  
Author(s):  
Manfred KUNZ ◽  
Gisela BLOSS ◽  
Reinhard GILLITZER ◽  
Gerd GROSS ◽  
Matthias GOEBELER ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Protein Kinase ◽  
Nuclear Factor Κb ◽  
Melanoma Cells ◽  
Mitogen Activated Protein Kinase ◽  
Nuclear Factor ◽  
Monocyte Chemoattractant Protein 1 ◽  
Monocyte Chemoattractant ◽  
Monocyte Chemoattractant Protein ◽  
Mitogen Activated Protein

Monocyte chemoattractant protein-1 (MCP-1) expression is found in malignant melanoma and melanoma metastases. Since areas of hypoxia/reoxygenation (H/R) are a common feature of malignant tumours and metastases, we addressed the question whether melanoma cells produce MCP-1 upon exposure to H/R. In the present study, we show that melanoma cells up-regulate MCP-1 mRNA and protein under H/R. By means of reporter gene analysis, we further demonstrate that H/R induces transcriptional activation of the MCP-1 promoter carrying a stimulatory protein-1 (SP1) and two nuclear factor-κB (NF-κB) binding motifs. Accordingly, H/R-stimulated melanoma cells showed enhanced binding activity of both transcription factors NF-κB and SP1 in electrophoretic mobility-shift assay. A common upstream activator of NF-κB, inhibitory κBα kinase, was not significantly activated under H/R conditions. Further analysis of upstream signalling events revealed that members of the mitogen-activated protein kinases family, namely extracellular signal-regulated protein kinase, c-Jun N-terminal kinase/ stress-activated protein kinase and p38 stress kinase, may be involved in MCP-1 transcriptional regulation under H/R. In summary, we conclude that H/R induces MCP-1 production in melanoma cells via the co-operative action of both transcription factors NF-κB and SP1, and involves mitogen-activated protein kinase signalling pathways. Functionally, H/R-induced MCP-1 production may contribute to tumour progression by committing selective pressure on tumour cells via chemoattraction and activation of tumour-infiltrating monocytes/macrophages.

scholarly journals Homocysteine stimulates nuclear factor κB activity and monocyte chemoattractant protein-1 expression in vascular smooth-muscle cells: a possible role for protein kinase C

2000 ◽  
Vol 352 (3) ◽  
pp. 817-826 ◽  
Author(s):  
Guoping WANG ◽  
Yaw L. SIOW ◽  
Karmin O
Keyword(s):  
Smooth Muscle ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Vascular Smooth Muscle Cells ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Monocyte Chemoattractant Protein 1 ◽  
Monocyte Chemoattractant ◽  
Monocyte Chemoattractant Protein ◽  
Kinase C

Monocyte chemoattractant protein-1 (MCP-1) is a potent chemokine that stimulates the migration of monocytes into the intima of arterial walls. Although many factors that induce MCP-1 expression have been identified, the effect of homocysteine on the expression of MCP-1 in atherogenesis and the underlying mechanisms are not entirely clear. The objective of the present study was to investigate the role of homocysteine in MCP-1 expression in human aorta vascular smooth-muscle cells (VSMCs). After VSMCs were incubated with homocysteine for various time periods, a nuclease protection assay and ELISA were performed. Homocysteine (0.05Ő0.2mM) significantly increased the expression of MCP-1 mRNA (up to 2.7-fold) and protein (up to 3.3-fold) in these cells. The increase in MCP-1 expression was associated with the activation of protein kinase C (PKC) as well as nuclear factor κB (NF-κB). Further investigation demonstrated that the activation of NF-κB was the result of a PKC-mediated reduction in the expression of inhibitory protein (IκBα) mRNA and protein in homocysteine-treated cells. Oxidative stress might also be involved in the activation of NF-κB by homocysteine in VSMCs. In conclusion, the present study has clearly demonstrated that the activation of PKC as well as superoxide production followed by activation of NF-κB is responsible for homocysteine-induced MCP-1 expression in VSMCs. These results suggest that homocysteine-stimulated MCP-1 expression via NF-κB activation may play an important role in atherogenesis.

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