title: Interaction of vascular smooth muscle cells and monocytes by soluble factors synergistically enhances IL-6 and MCP-1 production.
abstract: 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-alpha, and IL-6 completely blocked the synergism. IL-1, TNF-alpha, 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-alpha, 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.
authors.affiliation: Universitätsklinik und Poliklinik für Innere Medizin III, Martin-Luther-Universität Halle-Wittenberg, Halle (Saale), Germany.
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.forename: Adrian
authors.initials: A
authors.lastname: Frister
authors.forename: Song
authors.initials: S
authors.lastname: Wang
authors.forename: Andreas
authors.initials: A
authors.lastname: Ludwig
authors.forename: Hagen
authors.initials: H
authors.lastname: Behr
authors.forename: Susanna
authors.initials: S
authors.lastname: Pippig
authors.forename: Beibei
authors.initials: B
authors.lastname: Li
authors.forename: Andreas
authors.initials: A
authors.lastname: Simm
authors.forename: Britt
authors.initials: B
authors.lastname: Hofmann
authors.forename: Claudia
authors.initials: C
authors.lastname: Pilowski
authors.forename: Susanne
authors.initials: S
authors.lastname: Koch
authors.forename: Michael
authors.initials: M
authors.lastname: Buerke
authors.forename: Stefan
authors.initials: S
authors.lastname: Rose-John
authors.forename: Karl
authors.initials: K
authors.lastname: Werdan
authors.forename: Harald
authors.initials: H
authors.lastname: Loppnow
mesh_terms: D050197:Atherosclerosis / Q000378:metabolism / Q000473:pathology; D002450:Cell Communication / Q000502:physiology*; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism*; D018920:Coculture Techniques; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism*; D009000:Monocytes / Q000166:cytology* / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000378:metabolism; D010766:Phosphorylation; D012333:RNA, Messenger / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: C111835:CCL2 protein, human; D018932:Chemokine CCL2; D007375:Interleukin-1; D015850:Interleukin-6; D012333:RNA, Messenger; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D014409:Tumor Necrosis Factor-alpha