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PMID:10510402

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Citation

Klouche, M, Bhakdi, S, Hemmes, M and Rose-John, S (1999) Novel path to activation of vascular smooth muscle cells: up-regulation of gp130 creates an autocrine activation loop by IL-6 and its soluble receptor. J. Immunol. 163:4583-9

Abstract

This study describes a novel path to the activation of smooth muscle cells (SMC) by the IL-6/soluble IL-6 receptor (sIL-6R) system. Human vascular SMC constitutively express only scant amounts of IL-6R and so do not respond to stimulation with this cytokine. We show that SMC also do not constitutively express appreciable levels of gp130, which would render them sensitive to transsignaling by the IL-6/sIL-6R complex. Because gp130 is generally believed not to be subject to regulation, SMC would thus appear not to qualify as targets for the IL-6/sIL-6R system. However, we report that treatment of SMC with IL-6/sIL-6R provokes marked up-regulation of gp130 mRNA and surface protein expression. This is accompanied by secretion of IL-6 by the cells, so that an autocrine stimulation loop is created. In the wake of this self-sustaining system, there is a selective induction and secretion of MCP-1, up-regulation of ICAM-1, and marked cell proliferation. The study identifies SMC as the first example of cells in which gp130 expression is subject to substantive up-regulation, and discovers a novel amplification loop involving IL-6 and its soluble receptor that drives SMC into a proinflammatory state.

Links

PubMed

Keywords

Aged; Antigens, CD/biosynthesis; Autocrine Communication/immunology; Cell Division/immunology; Cells, Cultured; Chemokine CCL2/biosynthesis; Cytokine Receptor gp130; Female; Humans; Intercellular Adhesion Molecule-1/biosynthesis; Interleukin-6/biosynthesis; Interleukin-6/physiology; Macromolecular Substances; Male; Membrane Glycoproteins/biosynthesis; Muscle, Smooth, Vascular/cytology; Muscle, Smooth, Vascular/immunology; Muscle, Smooth, Vascular/metabolism; Receptors, Interleukin-6/physiology; Signal Transduction/immunology; Solubility; Up-Regulation/immunology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:IL6RA

involved_in

GO:0002548: monocyte chemotaxis

ECO:0000305: curator inference used in manual assertion

GO:0032722

P

Seeded From UniProt

complete

HUMAN:IL6RA

involved_in

GO:0032755: positive regulation of interleukin-6 production

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:IL6RA

involved_in

GO:0032722: positive regulation of chemokine production

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:IL6RA

involved_in

GO:0048661: positive regulation of smooth muscle cell proliferation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:IL6

involved_in

GO:0048661: positive regulation of smooth muscle cell proliferation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:IL6

involved_in

GO:0032755: positive regulation of interleukin-6 production

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:IL6

involved_in

GO:0032722: positive regulation of chemokine production

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:IL6

involved_in

GO:0002548: monocyte chemotaxis

ECO:0000305: curator inference used in manual assertion

GO:0032722

P

Seeded From UniProt

complete

See also

References

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