Ruef C, Kashgarian M, Coleman D L
Department of Medicine, Yale University School of Medicine, New Haven, Connecticut.
Am J Pathol. 1992 Aug;141(2):429-39.
Glomerulonephritis (GN) results in proliferation of mesangial cells (MC), infiltration of inflammatory cells, and accumulation of extracellular matrix (ECM) proteins in the mesangium. Locally secreted cytokines may stimulate MC growth or the secretion of inflammatory mediators by MC. Interleukin-6 (IL-6) may be an autocrine cofactor in the pathogenesis of mesangioproliferative GN. We studied the regulation of IL-6 secretion by MC in response to MC-derived cytokines and ECM proteins. IL-6 secretion is stimulated in a dose-dependent manner by IL-1 alpha, TNF-alpha, and PDGF. Constitutive and LPS-induced release of IL-6 by MCs is reduced on collagen type I (coll I) compared-with uncoated surfaces. IL-6 release on collagen type IV (coll IV), however, is enhanced. In addition, MC on coll I exhibit a sixfold higher growth rate than cells on uncoated surfaces. The reduction of cytokine secretion in parallel with the stimulation of MC growth by coll I suggests that exposure to coll I may result in a change from secretory to proliferative phenotype in vitro.
肾小球肾炎(GN)会导致系膜细胞(MC)增殖、炎症细胞浸润以及系膜中细胞外基质(ECM)蛋白的积累。局部分泌的细胞因子可能刺激MC生长或MC分泌炎症介质。白细胞介素-6(IL-6)可能是系膜增生性GN发病机制中的一种自分泌辅助因子。我们研究了MC对MC衍生的细胞因子和ECM蛋白的反应中IL-6分泌的调节。IL-1α、TNF-α和血小板衍生生长因子(PDGF)以剂量依赖的方式刺激IL-6分泌。与未包被的表面相比,MC在I型胶原(coll I)上组成性和脂多糖(LPS)诱导的IL-6释放减少。然而,MC在IV型胶原(coll IV)上的IL-6释放增强。此外,coll I上的MC比未包被表面上的细胞表现出高六倍的生长速率。coll I刺激MC生长的同时细胞因子分泌减少,这表明在体外暴露于coll I可能导致从分泌表型向增殖表型的转变。