Interleukin-4 modulates collagen synthesis by human mesangial cells in a type-specific manner.
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.
Nakazato
Y
Y
Department of Dermatology, School of Medicine, Keio University, Tokyo, Japan.
Okada
H
H
Tajima
S
S
Hayashida
T
T
Kanno
Y
Y
Suzuki
H
H
Saruta
T
T
D015153:Blotting, Western; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis*; D004797:Enzyme-Linked Immunosorbent Assay; D005920:Glomerular Mesangium / Q000378:metabolism*; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology*
D015847:Interleukin-4; D003094:Collagen