Matsuoka M, Pham N T, Tsukamoto H
Hepatopancreatic Research Laboratory, VA Medical Center, Martinez.
Liver. 1989 Apr;9(2):71-8. doi: 10.1111/j.1600-0676.1989.tb00382.x.
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)
贮脂细胞（FSCs）是位于肝血窦周的细胞，通常参与维生素A的代谢，有人认为它们也参与肝纤维化过程中的胶原合成。然而，调节贮脂细胞中胶原代谢的关键介质尚未明确。在成纤维细胞中，白细胞介素-1（IL-1）、肿瘤坏死因子α（TNFα）和转化生长因子β（TGFβ）已被证明可诱导胶原代谢和细胞增殖的多种调节。在本研究中，检测了这些细胞因子对培养的大鼠贮脂细胞调节胶原形成和增殖的能力。建立了贮脂细胞原代培养，并在无或有不同浓度的IL-1α、TNFα和TGFβ1的情况下进行孵育。用氚标记的脯氨酸和胸腺嘧啶来检测胶原形成和细胞增殖。IL-1α（2.5 - 10 U/ml）对贮脂细胞增殖有浓度依赖性刺激作用，与未处理的贮脂细胞相比，最大反应为160%。这种促有丝分裂作用导致净胶原形成略有但显著增加（15 - 20%）。然而，当该参数相对于DNA含量进行标准化时，IL-1α对胶原和非胶原蛋白质的形成均有显著抑制作用。TNFα也表现出类似的促有丝分裂作用，但对胶原形成的抑制更具选择性。相比之下，TGFβ1（0.01 - 1 ng/ml）特异性地使胶原形成增加了60 - 80%，新形成蛋白质中[3H]羟脯氨酸与[3H]脯氨酸的比例显著增加也证明了这一点。（摘要截短于250字）
