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

• 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: lung fibroblasts; prostacyclin; prostaglandins; pulmonary fibrosis; thromboxane
• Online Access: http://dx.doi.org/10.1186/rr166

<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]A₂) and antifibrotic (prostacyclin [PGI₂]) 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. 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; <it>P</it> = 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; <it>P</it> = 0.007) and the ratio of PGI₂ (as measured by its stable metabolite 6-keto-PGF_1α) 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; <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>