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Respiratory Research

, 3:9

First Online: 23 February 2002Received: 29 May 2001Revised: 14 November 2001Accepted: 21 December 2001

Abstract

BackgroundProstanoids 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 TXA2 and antifibrotic prostacyclin PGI2 prostaglandins PGs when compared with normal human lung fibroblasts HF-NL.

MethodsWe measured inducible cyclooxygenase COX-2 gene and protein expression, and a profile of prostanoids at baseline and after IL-1β stimulation.

ResultsIn 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-10 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-10 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.

ConclusionAn alteration in the balance of profibrotic and antifibrotic PGs in HF-IPF may play a role in the pathogeneses of IPF.

Keywordslung fibroblasts prostacyclin prostaglandins pulmonary fibrosis thromboxane AbbreviationsCOXcyclooxygenase

HFhuman fibroblasts

NLnormal lungs

IPFidiopathic pulmonary fibrosis

IFNinterferon

ILinterleukin

PGprostaglandin

TXthromboxane

PGI2prostacyclin

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Autor: Roberto Cruz-Gervis - Arlene A Stecenko - Ryszard Dworski - Kirk B Lane - James E Loyd - Richard Pierson - Gayle King -

Fuente: https://link.springer.com/



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