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人细胞系中补体生物合成的激素调节——I.雄激素和γ干扰素刺激人细胞系U937和HepG2中C1抑制剂的生物合成及基因表达。

Hormonal regulation of complement biosynthesis in human cell lines--I. Androgens and gamma-interferon stimulate the biosynthesis and gene expression of C1 inhibitor in human cell lines U937 and HepG2.

作者信息

Falus A, Fehér K G, Walcz E, Brozik M, Füst G, Hidvégi T, Fehér T, Merétey K

机构信息

Department of Immunology, National Institute of Rheumatology and Physiotherapy, Budapest, Hungary.

出版信息

Mol Immunol. 1990 Feb;27(2):191-5. doi: 10.1016/0161-5890(90)90114-f.

Abstract

C1 inhibitor (C1inh), a member of the serine protease inhibitor gene superfamily, is a glycosylated plasma protein inhibiting the proteolytic activities of C1r and C1s and involved in the regulation of coagulation, fibrinolysis and kinin-releasing systems. In this study, the in vitro effect of androgen hormones, dehydroepiandrosterone (DHEA), testosterone (TEST) and recombinant human gamma-interferon (gamma-IFN), has been determined on the production of C1inh in human cell lines. In both human monocytoid/histiocytoid cell line U937 and in hepatoma derived cell line HepG2, DHEA and TEST upregulated the gene expression and secretion of C1inh. The most pronounced effect was detected in the concn range 10(-7)-10(-9) M of the hormones. Under the same conditions DHEA and TEST had no detectable effect on the biosynthesis of C3, C2 and factor B by these cells, but DHEA at higher concn (10(-4) M) slightly increased that of C4 in HepG2 cells. Both in U937 and in HepG2 cells recombinant gamma-IFN markedly increased the gene expression and secretion of C1inh. This effect of gamma-IFN was abolished by histamine.

摘要

C1抑制剂(C1inh)是丝氨酸蛋白酶抑制剂基因超家族的成员之一,是一种糖基化血浆蛋白,可抑制C1r和C1s的蛋白水解活性,并参与凝血、纤维蛋白溶解和激肽释放系统的调节。在本研究中,已确定雄激素、脱氢表雄酮(DHEA)、睾酮(TEST)和重组人γ干扰素(γ-IFN)对人细胞系中C1inh产生的体外作用。在人单核细胞样/组织细胞样细胞系U937和肝癌衍生细胞系HepG2中,DHEA和TEST均上调了C1inh的基因表达和分泌。在激素浓度范围为10(-7)-10(-9)M时检测到最明显的效果。在相同条件下,DHEA和TEST对这些细胞的C3、C2和B因子的生物合成没有可检测到的影响,但较高浓度(10(-4)M)的DHEA可使HepG2细胞中的C4生物合成略有增加。在U937和HepG2细胞中,重组γ-IFN均显著增加了C1inh的基因表达和分泌。γ-IFN的这种作用被组胺消除。

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