Nakazato Y, Okada H, Tajima S, Hayashida T, Kanno Y, Suzuki H, Saruta T
Department of Dermatology, School of Medicine, Keio University, Tokyo, Japan.
Am J Physiol. 1996 Mar;270(3 Pt 2):F447-53. doi: 10.1152/ajprenal.1996.270.3.F447.
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.
多项研究表明白细胞介素（IL）-4参与了肾小球肾炎（GN）的病理生理过程。为阐明其在GN中可能的作用，我们研究了IL-4对人肾小球系膜细胞（MC）胶原积累的影响。在用IL-1α和/或IL-4孵育48小时后，通过蛋白质印迹法鉴定了可溶性和细胞相关形式的I、III和IV型胶原。IL-1α刺激I型和IV型胶原合成，对III型胶原合成无显著影响。相比之下，IL-4刺激III型胶原合成，而不影响I型和IV型胶原合成。酶联免疫吸附测定证实了IL-4对III型胶原分泌的剂量依赖性作用（10 ng/ml时为2.0倍）。重要的是，同时用IL-4处理可抑制IL-1α刺激的I型和IV型胶原合成。I型和III型前胶原mRNA的Northern分析显示了一致的结果。这些数据表明，IL-4选择性地刺激III型胶原合成，但也抑制IL-1α刺激的I型和IV型胶原合成。因此，IL-4可能与其他细胞因子协同作用，对肾小球疾病的病理变化产生影响。
