Altered prostanoid production by fibroblasts cultured from the lungs of human subjects with idiopathic pulmonary fibrosis
Open accessAbstract
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). CONCLUSION: An alteration in the balance of profibrotic and antifibrotic PGs in HF-IPF may play a role in the pathogeneses of IPF.
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Intranasal OSM in mice caused excessive lung collagen deposition that was independent of TGF-β, IL-4, IL-3, and STAT.
“OSM is a profibrotic glycoprotein – mice exposed to intranasal OSM demonstrated excessive collagen deposition in the lung, which was independent of TGF-β, IL-4, IL-3, and STAT, demonstrating the multiple pathways mediating pulmonary fibrosis [170–172].”
From Emerging pharmacological options in the treatment of idiopathic pulmonary fibrosis (IPF) (2024) · cites this paper as [172]
The Methods and Discussion describe prostanoid production in cultured human lung fibroblasts, not intranasal OSM exposure in mice. Searches for intranasal OSM and oncostatin M found no passage addressing mouse lung collagen deposition or its independence from TGF-β, IL-4, IL-3, and STAT. Page numbers were not available in our copy. (LLM, conf=0.76)
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- Authors
- Cruz-Gervis, R., Stecenko, A. A., Dworski, R., Lane, K. B., Loyd, J. E., Pierson, R., King, G., & Brigham, K. L.
- Affiliations
- Meharry Medical College (US)
- Vanderbilt University (US)
- Corresponding author
- Cruz-Gervis, Roberto
- Venue
- Respiratory Research
- Published
- 2002-02-23
- Volume
- 3
- Issue
- 1
- Pages
- 17-17
- ISSN
- 1465-9921 (ISSN-L)
- 1465-993X
- PMC
- PMC107846
- OpenAlex
- W1934130721
- Cited by
- 38
- References
- 28
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 1 · 2023: 1 · 2022: 3 · 2021: 1 · 2019: 2 · 2016: 1 · 2015: 2 · 2014: 3 · 2013: 1 · 2012: 1
- FWCI
- 1.37
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Respiratory Research (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institutes of Health (1r01hl063204-01)
- National Heart, Lung, and Blood Institute (T32HL007123, KO8 HL04402, R01 HL63204, HL07123)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Health Sciences › Medicine › Pharmacology › Inflammatory mediators and NSAID effects
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Pulmonary Hypertension Research and Treatments
- Keywords
- idiopathic pulmonary fibrosis, lung fibroblasts, prostanoids, prostaglandins, thromboxane A2, prostacyclin, cyclooxygenase-2, IL-1β, prostaglandin E2, thromboxane B2, 6-keto-PGF1 alpha, fibrogenesis, lung fibrosis pathogenesis, gene expression profiling, proteomics
- MeSH terms
- Adult, Aged, Cells, Cultured, Female, Fibroblasts, Humans, Interleukin-1, Male, Membrane Proteins, Middle Aged, Prostaglandins, Pulmonary Fibrosis, Cyclooxygenase 2
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