Potentiation of human lung fibroblast chemotaxis by the thromboxane A(2) analog U-46619.

T. Kohyama, X. Liu, F. Wen, H. J. Kim, H. Takizawa, S. Rennard
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引用次数: 9

Abstract

Fibroblast production of extracellular matrix is crucial not only for normal tissue development and maintenance of tissue structure but also for the repair and remodeling processes after injury. Thromboxane A(2) (TXA(2)) is a potent mediator in inflammatory processes. The aim of this study was to investigate the effect of TXA(2) on chemotaxis of human fetal lung (HFL-1) fibroblasts induced by human plasma fibronectin or platelet-derived growth factor BB (PDGF-BB). By using the blindwell chamber technique, the TXA(2) agonist U-46619 alone had no chemotactic activity. However, U-46619 (200 nmol/L) stimulated HFL-1 fibroblast chemotaxis to human plasma fibronectin (20 microg/mL; 161.8% +/- 13.4%; P <.005) and to PDGF-BB (10 ng/mL; 188.5% +/- 7.0%; P <.005). Checkerboard analysis of human plasma fibronectin-directed migration confirmed that the TXA(2) agonist increased both chemotaxis and chemokinesis. The stimulatory effect of the TXA(2) agonist was concentration dependent and increased with time. Another agent known for stimulating the protein kinase C pathway, phorbol 12-myristate 13-acetate (10(-8) mol/L), had a similar effect, stimulating chemotaxis to fibronectin (146.2% +/- 8.6%). The stimulatory effect of the TXA(2) agonist on HFL-1 fibroblast chemotaxis was inhibited by the synthetic thromboxane receptor antagonist SQ29,548 (10(-5) mol/L) and the protein kinase C inhibitor calphostin (10(-7) mol/L). In summary, TXA(2) appears to stimulate fibroblast chemotaxis to fibronectin and PDGF, perhaps by modulating the rate of fibroblast migration. Such an effect may contribute to regulation of wound healing and the development of fibrotic disorders.
血栓素A(2)类似物U-46619增强人肺成纤维细胞趋化性。
细胞外基质成纤维细胞的产生不仅对组织的正常发育和组织结构的维持至关重要,而且对损伤后的修复和重塑过程也至关重要。血栓素A(2) (TXA(2))是炎症过程中的有效介质。本研究的目的是探讨TXA(2)对人血浆纤维连接蛋白或血小板衍生生长因子BB (PDGF-BB)诱导的人胎儿肺(HFL-1)成纤维细胞趋化性的影响。盲眼实验结果表明,单独使用TXA(2)激动剂U-46619无趋化活性。然而,U-46619 (200 nmol/L)刺激了HFL-1成纤维细胞对人血浆纤维连接蛋白的趋化性(20 μ g/mL;161.8% +/- 13.4%;P < 0.005)和PDGF-BB (10 ng/mL;188.5%±7.0%;P < .005)。人血浆纤维连接蛋白定向迁移的棋盘分析证实,TXA(2)激动剂增加趋化性和趋化运动。TXA(2)激动剂的刺激作用呈浓度依赖性,且随时间延长而增强。另一种已知的刺激蛋白激酶C途径的药物是phorbol 12-肉豆蔻酸酯13-乙酸酯(10(-8)mol/L),具有类似的作用,刺激对纤维连接蛋白的趋化性(146.2% +/- 8.6%)。合成血栓素受体拮抗剂SQ29,548 (10(-5) mol/L)和蛋白激酶C抑制剂calphostin (10(-7) mol/L)可抑制TXA(2)激动剂对HFL-1成纤维细胞趋化作用。总之,TXA(2)似乎通过调节成纤维细胞迁移的速率,刺激成纤维细胞趋化纤维连接蛋白和PDGF。这种作用可能有助于调节伤口愈合和纤维化疾病的发展。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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