首页> 外文期刊>American Journal of Physiology >Bradykinin augments fibroblast-mediated contraction of released collagen gels.
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Bradykinin augments fibroblast-mediated contraction of released collagen gels.

机译:缓激肽增加了成纤维细胞介导的释放的胶原蛋白凝胶的收缩。

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摘要

Bradykinin is a multifunctional mediator of inflammation believed to have a role in asthma, a disorder associated with remodeling of extracellular connective tissue. Using contraction of collagen gels as an in vitro model of wound contraction, we assessed the effects of bradykinin tissue on remodeling. Human fetal lung fibroblasts were embedded in type I collagen gels and cultured for 5 days. After release, the floating gels were cultured in the presence of bradykinin. Bradykinin significantly stimulated contraction in a concentration- and time-dependent manner. Coincubation with phosphoramidon augmented the effect of 10(-9) and 10(-8) M bradykinin. A B2 receptor antagonist attenuated the effect of bradykinin, whereas a B1 receptor antagonist had no effect, suggesting that the effect is mediated by the B2 receptor. An inhibitor of intracellular Ca2+ mobilization abolished the response; addition of EGTA to the culture medium attenuated the contraction of control gels but did not modulate the response tobradykinin. In contrast, the phospholipase C inhibitor U-73122 and the protein kinase C inhibitors staurosporine and GF-109203X attenuated the responses. These data suggest that by augmenting the contractility of fibroblasts, bradykinin may have an important role in remodeling of extracellular matrix that may result in tissue dysfunction in chronic inflammatory diseases, such as asthma.
机译:缓激肽是炎症的多功能介体,据信在哮喘中起作用,哮喘是与细胞外结缔组织重塑相关的疾病。使用胶原蛋白凝胶的收缩作为伤口收缩的体外模型,我们评估了缓激肽组织对重塑的影响。将人胎儿肺成纤维细胞包埋在I型胶原凝胶中,并培养5天。释放后,在缓激肽存在下培养浮动凝胶。缓激肽以浓度和时间依赖性方式显着刺激收缩。与磷酰胺共孵育可增强10(-9)和10(-8)M缓激肽的作用。 B2受体拮抗剂减弱了缓激肽的作用,而B1受体拮抗剂则没有作用,表明该作用是由B2受体介导的。细胞内Ca2 +动员的抑制剂消除了该反应。向培养基中加入EGTA可减弱对照凝胶的收缩,但不能调节对缓激肽的反应。相反,磷脂酶C抑制剂U-73122和蛋白激酶C抑制剂星形孢菌素和GF-109203X减弱了反应。这些数据表明,缓激肽可能通过增强成纤维细胞的收缩性而在细胞外基质的重塑中起重要作用,而细胞外基质的重塑可能导致慢性炎症性疾病(如哮喘)中的组织功能障碍。

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