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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BMC
2002-02-01
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Series: | Respiratory Research |
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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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issn | 1465-9921 |
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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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