Altered prostanoid production by fibroblasts cultured from the lungs of human subjects with idiopathic pulmonary fibrosis.
Altered prostanoid production by fibroblasts cultured from the lungs of human subjects with idiopathic pulmonary fibrosis.
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DOI：
10.1186/rr166
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发表时间：
2002
影响因子：
5.8
通讯作者：
Brigham KL
中科院分区：
文献类型：
--
作者：
Cruz-Gervis R;Stecenko AA;Dworski R;Lane KB;Loyd JE;Pierson R;King G;Brigham KL
已知前列腺素类参与纤维形成过程。由于肺成纤维细胞产生前列腺素类，并被认为在特发性肺纤维化（IPF）的发病机制中发挥核心作用，我们假设从IPF患者肺培养的成纤维细胞（HF）（HF-IPF）与正常人肺成纤维细胞（HF-NL）相比，促纤维化（血栓烷[TX]A2）和抗纤维化（前列环素[PGI 2]）前列腺素（PG）之间的平衡发生改变。我们测量了诱导型环氧合酶（考克斯）-2基因和蛋白表达，以及基线和IL-1β刺激后的前列腺素谱。在HF-IPF和HF-NL中，基线时均未检测到考克斯-2表达，但IL-1β显着上调。在IL-1β刺激的细胞中，PGE 2是主要的考克斯产物，HF-IPF和HF-NL之间无显著差异（分别为28.35 [9.09-89.09] vs. 17.12 [8.58-29.33] ng/106 cells/30 min; P = 0.25）。TXB2与HF-NL相比，IL-1β刺激的HF-IPF（TXA 2的稳定代谢产物）的产生显著更高（1.92 [1.27-2.57] vs. 0.61 [0.21-1.64] ng/106 cells/30 min; P = 0.007）和PGI 2（通过其稳定代谢产物6-keto-PGF 1 α测定）对TXB 2的影响在基线时显著降低（HF-NL中0.08 [0.04-0.52] vs. 0.12 [0.11-0.89]; P = 0.028）和IL-1β刺激（HF-NL中0.24 [0.05-1.53] vs. 1.08 [0.51-3.79]; P = 0.09）。HF-IPF中促纤维化和抗纤维化PG平衡的改变可能在IPF的发病机制中发挥作用。
Prostanoids are known to participate in the process of fibrogenesis. Because lung fibroblasts produce prostanoids and are believed to play a central role in the pathogenesis of idiopathic pulmonary fibrosis (IPF), we hypothesized that fibroblasts (HF) cultured from the lungs of patients with IPF (HF-IPF) have an altered balance between profibrotic (thromboxane [TX]A2) and antifibrotic (prostacyclin [PGI2]) prostaglandins (PGs) when compared with normal human lung fibroblasts (HF-NL). We measured inducible cyclooxygenase (COX)-2 gene and protein expression, and a profile of prostanoids at baseline and after IL-1β stimulation. In both HF-IPF and HF-NL COX-2 expression was undetectable at baseline, but was significantly upregulated by IL-1β. PGE2 was the predominant COX product in IL-1β-stimulated cells with no significant difference between HF-IPF and HF-NL (28.35 [9.09–89.09] vs. 17.12 [8.58–29.33] ng/106 cells/30 min, respectively; P = 0.25). TXB2 (the stable metabolite of TXA2) production was significantly higher in IL-1β-stimulated HF-IPF compared to HF-NL (1.92 [1.27–2.57] vs. 0.61 [0.21–1.64] ng/106 cells/30 min, respectively; P = 0.007) and the ratio of PGI2 (as measured by its stable metabolite 6-keto-PGF1α) to TXB2 was significantly lower at baseline in HF-IPF (0.08 [0.04–0.52] vs. 0.12 [0.11–0.89] in HF-NL; P = 0.028) and with IL-1β stimulation (0.24 [0.05–1.53] vs. 1.08 [0.51–3.79] in HF-NL; P = 0.09). An alteration in the balance of profibrotic and antifibrotic PGs in HF-IPF may play a role in the pathogeneses of IPF.