title: Altered prostanoid production by fibroblasts cultured from the lungs of human subjects with idiopathic pulmonary fibrosis.
abstract: BACKGROUND
  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).
  
  
  METHODS
  We measured inducible cyclooxygenase (COX)-2 gene and protein expression, and a profile of prostanoids at baseline and after IL-1beta stimulation.
  
  
  RESULTS
  In both HF-IPF and HF-NL COX-2 expression was undetectable at baseline, but was significantly upregulated by IL-1beta. PGE2 was the predominant COX product in IL-1beta-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(6) cells/30 min, respectively; P = 0.25). TXB2 (the stable metabolite of TXA2) production was significantly higher in IL-1beta-stimulated HF-IPF compared to HF-NL (1.92 [1.27-2.57] vs. 0.61 [0.21-1.64] ng/10(6) cells/30 min, respectively; P = 0.007) and the ratio of PGI2 (as measured by its stable metabolite 6-keto-PGF1alpha) 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-1beta stimulation (0.24 [0.05-1.53] vs. 1.08 [0.51-3.79] in HF-NL; P = 0.09).
  
  
  CONCLUSIONS
  An alteration in the balance of profibrotic and antifibrotic PGs in HF-IPF may play a role in the pathogeneses of IPF.
authors: Center for Lung Research, Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, Vanderbilt University, Nashville, Tennessee, USA. roberto.cruz-gervis@mcmail.vanderbilt.edu
authors: Roberto
authors: R
authors: Cruz-Gervis
authors: Arlene A
authors: AA
authors: Stecenko
authors: Ryszard
authors: R
authors: Dworski
authors: Kirk B
authors: KB
authors: Lane
authors: James E
authors: JE
authors: Loyd
authors: Richard
authors: R
authors: Pierson
authors: Gayle
authors: G
authors: King
authors: Kenneth L
authors: KL
authors: Brigham
mesh_terms: D000328:Adult; D000368:Aged; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics; D008875:Middle Aged; D011453:Prostaglandins / Q000096:biosynthesis* / Q000235:genetics; D011658:Pulmonary Fibrosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: D007375:Interleukin-1; D008565:Membrane Proteins; D011453:Prostaglandins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human