Differential effects of interleukin-1 alpha, tumor necrosis factor alpha, and transforming growth factor beta 1 on cell proliferation and collagen formation by cultured fat-storing cells

Abstract

Fat-storing cells (FSCs), perisinusoidal cells which normally participate in metabolism of vitamin A, have been suggested to participate in collagen synthesis in fibrotic liver. However, key mediators which regulate collagen metabolism in FSCs are yet to be elucidated. In fibroblasts, Interleukin-1 (IL-1), Tumor Necrosis Factor alpha (TNF alpha), and Transforming Growth Factor beta (TGF beta) have been shown to induce diverse modulations of collagen metabolism and cell proliferation. In the present study, these cytokines were tested for their abilities to regulate collagen formation and proliferation by cultured rat FSCs. FSCs primary culture was established and incubated in the absence or presence of various concentrations of IL-1 alpha, TNF alpha, and TGF beta 1. Tritiated proline and thymidine were used to examine collagen formation and cell proliferation. IL-1 alpha (2.5-10 U/ml) had a concentration-dependent stimulatory effect on FSC proliferation with a maximal response of 160% compared to that of untreated FSCs. This mitogenic effect resulted in slight but significant increases (15-20%) in the net collagen formation. However, when this parameter was standardized relative to DNA content, significant inhibition of both collagen and noncollagen protein formation by IL-1 alpha was demonstrated. TNF alpha also exhibited a similar mitogenic effect but induced a more selective inhibition of collagen formation. In contrast, TGF beta 1 (0.01-1 ng/ml) specifically enhanced collagen formation by 60-80%, as also evidenced by significant increases in the ratio of [3H]hydroxyproline to [3H]proline incorporated in newly formed proteins.(ABSTRACT TRUNCATED AT 250 WORDS)