Activation of PKC-beta isoforms mediates HNE-induced MCP-1 release by macrophages |
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Authors: | Nitti M Domenicotti C d'Abramo C Assereto S Cottalasso D Melloni E Poli G Biasi F Marinari U M Pronzato M A |
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Institution: | Department of Experimental Medicine, General Pathology Section, University of Genoa, Via L.B. Alberti, 2, 16132 Genoa, Italy. |
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Abstract: | 4-Hydroxynonenal (HNE) in the concentration range detectable in many pathophysiologic conditions is able to modulate signal transduction cascades and gene expression. Here, we report the stimulating effect of 1 microM HNE on the release of the monocyte chemotactic protein-1 (MCP-1) by murine macrophages. MCP-1-increased export following 1-h cell treatment with HNE proved to be comparable to that exerted by standard amounts of bacterial lipopolysaccharide (LPS). However, the key molecular event in HNE-induced secretion of MCP-1 appeared to be the increased activity of beta-PKC isoforms, which are recognized as playing a role in the regulation of cell protein transport and secretion. On the other hand, in LPS-stimulated cells, the delta isoform was seen to be involved and was probably related to LPS-mediated effects on MCP-1 expression and synthesis. In conclusion, HNE might interact with other pro-inflammatory stimuli, like LPS, in a concerted amplification of MCP-1 production and secretion. |
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Keywords: | PKC isoenzymes 4-Hydroxynonenal MCP-1 Cell signaling Macrophages |
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