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This Article Full Text Full Text (PDF) All Versions of this Article: 296/4/H987    most recent 01158.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Chen, L. Articles by Loppnow, H. Search for Related Content PubMed PubMed Citation Articles by Chen, L. Articles by Loppnow, H.

Interaction of vascular smooth muscle cells and monocytes by soluble factors synergistically enhances IL-6 and MCP-1 production

¹Universitätsklinik und Poliklinik für Innere Medizin III, Martin-Luther-Universität Halle-Wittenberg, Halle (Saale); ²Institut für Pharmakologie und Toxikologie, Universitätsklinikum Aachen, Aachen; ³Universitätsklinik und Poliklinik für Herz- und Thoraxchirurgie, Martin-Luther-Universität Halle-Wittenberg, Halle (Saale); and ⁴Biochemisches Institut, Christian-Albrechts-Universität, Kiel, Germany

Submitted 3 November 2008 ; accepted in final form 15 January 2009

Inflammatory mechanisms contribute to atherogenesis. Monocyte chemoattractant protein (MCP)-1 and IL-6 are potent mediators of inflammation. Both contribute to early atherogenesis by luring monocytes and regulating cell functions in the vessel wall. MCP-1 and IL-6 production resulting from the interaction of invading monocytes with local vessel wall cells may accelerate atherosclerosis. We investigated the influence of the interaction of human vascular smooth muscle cells (SMCs) with human mononuclear cells (MNCs) or monocytes on IL-6 and MCP-1 production in a coculture model. Interaction synergistically enhanced IL-6 and MCP-1 production (up to 30- and 10-fold, respectively) compared with separately cultured cells. This enhancement was mediated by CD14-positive monocytes. It was dependent on the SMC-to-MNC/monocyte ratio, and as few as 0.2 monocytes/SMC induced the synergism. Synergistic IL-6 production was observed at the protein, mRNA, and functional level. It was mediated by soluble factors, and simultaneous inhibition of IL-1, TNF-, and IL-6 completely blocked the synergism. IL-1, TNF-, and IL-6 were present in the cultures. Blockade of the synergism by soluble glycoprotein 130Fc/soluble IL-6 receptor, as well as the induction of synergistic IL-6 production by costimulation of SMCs with IL-1, TNF-, and hyper-IL-6, suggested the involvement of IL-6 trans-signaling. The contribution of IL-6 was consistent with enhanced STAT3 phosphorylation. The present data suggest that SMC/monocyte interactions may augment the proinflammatory status in the tissue, contributing to the acceleration of early atherogenesis.

inflammation; monocytes/macrophages; chemokines; cytokines; lipopolysaccharide; interleukin-6; monocyte chemoattractant protein-1