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γ-干扰素对人腹膜和成纤维细胞中缺氧刺激的细胞外基质表达的逆转作用。

Effects of interferon-gamma reverse hypoxia-stimulated extracellular matrix expression in human peritoneal and adhesion fibroblasts.

作者信息

Saed Ghassan M, Diamond Michael P

机构信息

Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Wayne State University School of Medicine-Detroit Medical Center, Detroit, Michigan, USA.

出版信息

Fertil Steril. 2006 Apr;85 Suppl 1:1300-5. doi: 10.1016/j.fertnstert.2005.12.013.

Abstract

OBJECTIVE

To determine the response of adhesion and normal peritoneal fibroblasts to interferon-gamma (IFN-gamma) under normal and hypoxic conditions.

DESIGN

Prospective experimental study.

SETTING

University medical center.

PATIENT(S): Primary cultures of fibroblasts established from peritoneal and adhesion tissue of the same patients.

INTERVENTION(S): Hypoxia and IFN-gamma treatment of the primary cultured fibroblasts.

MAIN OUTCOME MEASURE(S): Primary cultures of fibroblasts were established from peritoneal and adhesion tissues of the same patients (n = 5). The expression of extracellular matrix components (type I collagen and fibronectin) in adhesion and peritoneal fibroblasts under normal (20% O2) and hypoxic (2% O2) conditions was evaluated by multiplex reverse-transcription polymerase chain reaction analysis.

RESULT(S): Adhesion fibroblasts (ADF) have increased basal levels of type I collagen as compared with normal peritoneal fibroblasts (NF). Interferon-gamma treatment resulted in a dose-response decrease in type I collagen and fibronectin mRNA levels in both ADF and NF. Hypoxia treatment resulted in a time-response increase in type I collagen and fibronectin mRNA levels in NF and ADF. Hypoxia had no effect on type I collagen and fibronectin mRNA levels in the presence of increasing dose of IFN-gamma in both NF and ADF. Interferon-gamma can block the stimulating effects of hypoxia on type I collagen expression, supporting the antifibrogenic nature of this cytokine.

CONCLUSION(S): Understanding the mechanism by which IFN-gamma exerts its effect will be important in the utilization of this cytokine as a therapy for postoperative adhesion and tissue fibrosis.

摘要

目的

确定在正常和缺氧条件下,粘连和成纤维细胞对γ干扰素(IFN-γ)的反应。

设计

前瞻性实验研究。

地点

大学医学中心。

患者

从同一患者的腹膜和粘连组织建立的成纤维细胞原代培养物。

干预措施

对原代培养的成纤维细胞进行缺氧和IFN-γ处理。

主要观察指标

从同一患者(n = 5)的腹膜和粘连组织建立成纤维细胞原代培养物。通过多重逆转录聚合酶链反应分析评估正常(20%氧气)和缺氧(2%氧气)条件下粘连和成纤维细胞中细胞外基质成分(I型胶原和纤连蛋白)的表达。

结果

与正常腹膜成纤维细胞(NF)相比,粘连成纤维细胞(ADF)的I型胶原基础水平升高。γ干扰素处理导致ADF和NF中I型胶原和纤连蛋白mRNA水平呈剂量反应性下降。缺氧处理导致NF和ADF中I型胶原和纤连蛋白mRNA水平呈时间反应性增加。在NF和ADF中,在IFN-γ剂量增加的情况下,缺氧对I型胶原和纤连蛋白mRNA水平没有影响。γ干扰素可以阻断缺氧对I型胶原表达的刺激作用,支持这种细胞因子的抗纤维化性质。

结论

了解IFN-γ发挥作用的机制对于将这种细胞因子用作术后粘连和组织纤维化的治疗方法具有重要意义。

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