AJP - Renal Physiology, Vol 270, Issue 3 447-F453, Copyright © 1996 by American Physiological Society

ARTICLES

Interleukin-4 modulates collagen synthesis by human mesangial cells in a type-specific manner

Y. Nakazato, H. Okada, S. Tajima, T. Hayashida, Y. Kanno, H. Suzuki and T. Saruta
Department of Dermatology, School of Medicine, Keio University, Tokyo, Japan.

Several studies have suggested an involvement of interleukin (IL)-4 in the pathophysiology of glomerulonephritis (GN). To elucidate its possible role in GN, we have investigated the effect of IL-4 on collagen accumulation by human mesangial cells (MC). After incubation with IL-1 alpha and/or IL-4 for 48 h, type I, III, and IV collagens in both soluble and cell-associated forms were identified by Western blotting. IL-1 alpha stimulated type I and IV collagen synthesis, lacking significant effect on type III collagen synthesis. In contrast, IL-4 stimulated type III collagen synthesis without affecting type I and type IV synthesis. Enzyme-linked immunosorbent assay confirmed the dose-dependent effect of IL-4 on collagen type III secretion (2.0-fold at 10 ng/ml). Importantly, IL-1 alpha-stimulated type I and IV collagen synthesis was suppressed by concomitant IL-4 treatment. Northern analysis of type I and III procollagen mRNAs displayed consistent results. These data indicate that IL-4 selectively stimulates type III collagen synthesis but also suppresses IL-1 alpha-stimulated type I and IV collagen synthesis. Therefore IL-4 could potentially contribute to the pathological changes in glomerular diseases in cooperate with other cytokines.

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