Interleukin-1 upregulates decorin production by arterial smooth muscle cells.

Abstract

An increase in dermatan sulfate-proteoglycan (DSPG) production occurs in cultured aortic smooth muscle cells exposed to macrophage-conditioned media, an effect that is abrogated by an antibody to interleukin-1 (IL-1). To determine which DSPG gene was regulated, cultured arterial smooth muscle cells from monkeys (Macaca fascicularis) were treated with 0 to 500 pg/mL human recombinant IL-1 alpha or IL-1 beta in the presence of [35S]sulfate and [3H]serine. Proteoglycans were isolated from the culture media and purified by selective precipitation and chromatography. Both recombinant IL-1 alpha and IL-1 beta caused a dose-response increase in DSPG production. Northern blot analysis of mRNA isolated from the cells identified 1.6-kb and 2.6-kb transcripts homologous to the cDNA encoding human decorin and biglycan, respectively. IL-1 treatment resulted in increases in the steady-state level of decorin mRNA as high as fourfold to sixfold at 500 pg/mL recombinant IL-beta. By contrast, mRNA for biglycan was unchanged. Western blotting confirmed a specific enhancement of the 45-kD decorin core protein. These data indicate that IL-1 has differential effects on the two DSPG genes and suggest that macrophages may be capable of modifying the extracellular matrix of the artery wall by enhancing smooth muscle cell decorin production.