title: Silica-stimulated monocytes release fibroblast proliferation factors identical to interleukin 1. A potential role for interleukin 1 in the pathogenesis of silicosis.
abstract: Previous study strongly suggests that silicotic fibrosis is mediated by macrophages and their soluble mediators. The biochemical properties of the mediators involved in silicotic fibrosis, however, are as yet ill defined. The current study, therefore, determined whether human monocyte-macrophages treated with fibrogenic silica dust released factors capable of activating fibroblasts as measured by an increase in fibroblast proliferation. Silica, but not nonfibrogenic diamond dust, stimulated the release of fibroblast proliferation factors. Moreover, the level of fibroblast proliferation activity was comparable with the level of thymocyte proliferation (interleukin-1) activity in the same culture supernatants. The factors responsible for these seemingly diverse activities were found to behave identically when analyzed by gel filtration chromatography, size exclusion chromatography, isoelectrofocusing, ion exchange chromatography, and hydrophobic chromatography. Moreover, the response of these factors to four different proteases and heat (56 degrees C) was also identical, which shows that their comigration on various separation media could not be explained by noncovalent interaction between otherwise unrelated species. The data demonstrate that a monocyte-derived thymocyte proliferation factor having the molecular properties of interleukin 1 is capable of regulating fibroblast proliferation. In silicosis and other fibrotic diseases, the local release of interleukin 1 may contribute to abnormal connective tissue deposition by stimulating fibroblast proliferation, and thereby, amplifying other signals stimulating the synthesis of connective tissue components.
mesh_terms: D002478:Cells, Cultured; D004391:Dust; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008903:Minerals / Q000633:toxicity; D009000:Monocytes / Q000187:drug effects*; D010447:Peptide Hydrolases / Q000378:metabolism; D012822:Silicon Dioxide / Q000633:toxicity*; D012829:Silicosis / Q000209:etiology*
chemical_list: D004391:Dust; D007375:Interleukin-1; D008903:Minerals; D012822:Silicon Dioxide; D010447:Peptide Hydrolases