Glomerular Mesangial Cells

Glomerular mesangial cell (MC)-derived IL-1 may be an important factor in the development of the hypercellularity and sclerosis characteristic of many forms of glomerulonephritis. To define the regulation of IL-I synthesis by human MC, Northern blot analyses were performed using specific probes for monocytic IL-1 a and 8 mRNA. Proliferating MC expressed mRNA for both IL-1 a and ft, whereas nonproliferating MC contained no detectable IL-1 mRNA. Synchronized MC expressed IL-i a and ft mRNA within 2 h of stimulation with serum. This serum effect could be reproduced with platelet-derived growth factor and epidermal growth factor. Immune precipitations of 35S-methionine-labeled cells indicate that the mesangial IL-1 is synthesized as a 33-kD precursor protein with a p1 of 7.2. Extracellular mesangial IL-1 has a pl of 7.0 and molecular weight of 17 kD, consistent with its identification as ILfl. Cellular proliferation in glomerular disease may be driven in part by peptide growth factor-mediated induction of mesangial IL-1 gene expression and protein synthesis.