Altered prostanoid production by fibroblasts cultured from the lungs of human subjects with idiopathic pulmonary fibrosis

<p>Abstract</p> <p>Background</p> <p>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 tha...

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Main Authors: Pierson Richard, Loyd James E, Lane Kirk B, Dworski Ryszard, Stecenko Arlene A, Cruz-Gervis Roberto, King Gayle, Brigham Kenneth L
Format: Article
Language:English
Published: BMC 2002-02-01
Series:Respiratory Research
Subjects:
Online Access:http://dx.doi.org/10.1186/rr166
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author Pierson Richard
Loyd James E
Lane Kirk B
Dworski Ryszard
Stecenko Arlene A
Cruz-Gervis Roberto
King Gayle
Brigham Kenneth L
author_facet Pierson Richard
Loyd James E
Lane Kirk B
Dworski Ryszard
Stecenko Arlene A
Cruz-Gervis Roberto
King Gayle
Brigham Kenneth L
author_sort Pierson Richard
collection DOAJ
description <p>Abstract</p> <p>Background</p> <p>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]A<sub>2</sub>) and antifibrotic (prostacyclin [PGI<sub>2</sub>]) prostaglandins (PGs) when compared with normal human lung fibroblasts (HF-NL).</p> <p>Methods</p> <p>We measured inducible cyclooxygenase (COX)-2 gene and protein expression, and a profile of prostanoids at baseline and after IL-1β stimulation.</p> <p>Results</p> <p>In both HF-IPF and HF-NL COX-2 expression was undetectable at baseline, but was significantly upregulated by IL-1β. PGE<sub>2</sub> 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<sup>6</sup> cells/30 min, respectively; <it>P</it> = 0.25). TXB<sub>2</sub> (the stable metabolite of TXA<sub>2</sub>) 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<sup>6</sup> cells/30 min, respectively; <it>P</it> = 0.007) and the ratio of PGI<sub>2</sub> (as measured by its stable metabolite 6-keto-PGF<sub>1α</sub>) to TXB<sub>2</sub> was significantly lower at baseline in HF-IPF (0.08 [0.04–0.52] vs. 0.12 [0.11–0.89] in HF-NL; <it>P</it> = 0.028) and with IL-1β stimulation (0.24 [0.05–1.53] vs. 1.08 [0.51–3.79] in HF-NL; <it>P</it> = 0.09).</p> <p>Conclusion</p> <p>An alteration in the balance of profibrotic and antifibrotic PGs in HF-IPF may play a role in the pathogeneses of IPF.</p>
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spelling doaj.art-41eeefec71294be49c3f2c426fc4f4db2022-12-22T02:12:30ZengBMCRespiratory Research1465-99212002-02-01311710.1186/rr166Altered prostanoid production by fibroblasts cultured from the lungs of human subjects with idiopathic pulmonary fibrosisPierson RichardLoyd James ELane Kirk BDworski RyszardStecenko Arlene ACruz-Gervis RobertoKing GayleBrigham Kenneth L<p>Abstract</p> <p>Background</p> <p>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]A<sub>2</sub>) and antifibrotic (prostacyclin [PGI<sub>2</sub>]) prostaglandins (PGs) when compared with normal human lung fibroblasts (HF-NL).</p> <p>Methods</p> <p>We measured inducible cyclooxygenase (COX)-2 gene and protein expression, and a profile of prostanoids at baseline and after IL-1β stimulation.</p> <p>Results</p> <p>In both HF-IPF and HF-NL COX-2 expression was undetectable at baseline, but was significantly upregulated by IL-1β. PGE<sub>2</sub> 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<sup>6</sup> cells/30 min, respectively; <it>P</it> = 0.25). TXB<sub>2</sub> (the stable metabolite of TXA<sub>2</sub>) 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<sup>6</sup> cells/30 min, respectively; <it>P</it> = 0.007) and the ratio of PGI<sub>2</sub> (as measured by its stable metabolite 6-keto-PGF<sub>1α</sub>) to TXB<sub>2</sub> was significantly lower at baseline in HF-IPF (0.08 [0.04–0.52] vs. 0.12 [0.11–0.89] in HF-NL; <it>P</it> = 0.028) and with IL-1β stimulation (0.24 [0.05–1.53] vs. 1.08 [0.51–3.79] in HF-NL; <it>P</it> = 0.09).</p> <p>Conclusion</p> <p>An alteration in the balance of profibrotic and antifibrotic PGs in HF-IPF may play a role in the pathogeneses of IPF.</p>http://dx.doi.org/10.1186/rr166lung fibroblastsprostacyclinprostaglandinspulmonary fibrosisthromboxane
spellingShingle Pierson Richard
Loyd James E
Lane Kirk B
Dworski Ryszard
Stecenko Arlene A
Cruz-Gervis Roberto
King Gayle
Brigham Kenneth L
Altered prostanoid production by fibroblasts cultured from the lungs of human subjects with idiopathic pulmonary fibrosis
Respiratory Research
lung fibroblasts
prostacyclin
prostaglandins
pulmonary fibrosis
thromboxane
title Altered prostanoid production by fibroblasts cultured from the lungs of human subjects with idiopathic pulmonary fibrosis
title_full Altered prostanoid production by fibroblasts cultured from the lungs of human subjects with idiopathic pulmonary fibrosis
title_fullStr Altered prostanoid production by fibroblasts cultured from the lungs of human subjects with idiopathic pulmonary fibrosis
title_full_unstemmed Altered prostanoid production by fibroblasts cultured from the lungs of human subjects with idiopathic pulmonary fibrosis
title_short Altered prostanoid production by fibroblasts cultured from the lungs of human subjects with idiopathic pulmonary fibrosis
title_sort altered prostanoid production by fibroblasts cultured from the lungs of human subjects with idiopathic pulmonary fibrosis
topic lung fibroblasts
prostacyclin
prostaglandins
pulmonary fibrosis
thromboxane
url http://dx.doi.org/10.1186/rr166
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