Activation of MCP-1 gene expression is mediated through multiple signaling pathways.

Multiple signal transduction pathways including protein kinase C, tyrosine phosphorylation, and an independent third signaling mechanism are involved in the activation of monocyte chemotactic protein-1 gene. Northern blot analysis showed that the incubation of endothelial cell with dioctanoylglycerol induced maximum level of monocyte chemotactic protein-1 transcripts. The TPA-induced monocyte chemotactic protein-1 expression was abolished by treating the cells with both staurosporine and genistein; however, only a portion of the LPS-induced expression was inhibited by staurosporine/genistein. This is in accordance with the observation that LPS induced the expression of monocyte chemotactic protein-1 in desensitized cells. Thus, a third signal transduction pathway other than protein kinase C or tyrosine kinase is involved in the LPS-induced monocyte chemotactic protein-1 expression in human endothelial cell.