title: Human vascular smooth muscle cells produce an intracellular form of interleukin-1 receptor antagonist.
abstract: Interleukin-1 (IL-1) is a proinflammatory monocyte- and macrophage-derived cytokine that has potent vasorelaxant effects on vascular smooth muscle cells (VSMC). VSMC themselves also express both IL-1 alpha- and beta-genes, suggesting that IL-1 may be an autocrine regulator of VSMC function. The present study demonstrates that human saphenous vein VSMC (HSVSMC) produce IL-1 receptor antagonist (IL-1Ra), a specific inhibitor of IL-1 action. IL-1Ra was produced constitutively in most experiments, and its production was upregulated by phorbol 12-myristate 13-acetate and by IL-1 beta. IL-1Ra produced by HSVSMC remained predominately cell associated and was not detectable extracellularly. Furthermore, reverse transcription-polymerase chain reaction analysis and cDNA sequencing indicated that HSVSMC express the alternatively spliced form of IL-1Ra which lacks the signal peptide present in secreted IL-1Ra. HSVSMC also produced IL-1 alpha and the precursor form but not the mature form of IL-1 beta. These results suggest that HSVSMC lack active IL-1 beta-converting enzyme. Like IL-1Ra, IL-1 beta precursor and IL-1 alpha remained cell associated, predominately in the cytosolic fraction. IL-1 beta induced production of both IL-1Ra and IL-1 alpha at each time point and concentration tested. In contrast, platelet-derived growth factor and transforming growth factor-beta augmented production of IL-1Ra, but not that of IL-1 alpha. These results are suggestive of an autocrine role for cell-associated IL-1Ra, as well as for IL-1 alpha and IL-1 beta, in the regulation of VSMC function.
mesh_terms: D001483:Base Sequence; D002478:Cells, Cultured; D003600:Cytosol / Q000378:metabolism; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism / Q000494:pharmacology; D007425:Intracellular Membranes / Q000378:metabolism*; D015335:Molecular Probes / Q000235:genetics; D008969:Molecular Sequence Data; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D011498:Protein Precursors / Q000378:metabolism; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors*; D014158:Transcription, Genetic; D016212:Transforming Growth Factor beta / Q000494:pharmacology
chemical_list: D007375:Interleukin-1; D015335:Molecular Probes; D010982:Platelet-Derived Growth Factor; D011498:Protein Precursors; D017472:Receptors, Interleukin-1; D016212:Transforming Growth Factor beta