Altered prostanoid production by fibroblasts cultured from the lungs of human subjects with idiopathic pulmonary fibrosis.
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.
Cruz-Gervis
Roberto
R
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
Stecenko
Arlene A
AA
Dworski
Ryszard
R
Lane
Kirk B
KB
Loyd
James E
JE
Pierson
Richard
R
King
Gayle
G
Brigham
Kenneth L
KL
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
D007375:Interleukin-1; D008565:Membrane Proteins; D011453:Prostaglandins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human