Resistance of fibrogenic responses to glucocorticoid and 2-methoxyestradiol in bleomycin-induced lung fibrosis in mice
- PMID: 17823636
- DOI: 10.1139/Y07-065
Resistance of fibrogenic responses to glucocorticoid and 2-methoxyestradiol in bleomycin-induced lung fibrosis in mice
Abstract
Bleomycin-induced lung fibrosis in mice reproduces some key features of pulmonary fibrosis in humans including alveolar inflammation, myofibroblast proliferation, and collagen deposition. Glucocorticoids have been used as first-line therapy for the treatment of lung fibrosis, although their clinical efficacy is equivocal. We examined the effect of the glucocorticoid, methylprednisolone (MP), and the estrogen metabolite, 2-methoxyestradiol (2MEO) on bleomycin-induced bronchoalveolar inflammation, fibrosis, and changes in lung function. The characterization of the time-course of the bleomycin-induced fibrosis indicated that lung dry mass and hydroxyproline content showed less variance than histopathological assessment of fibrosis. The bleomycin-induced increases in bronchoalveolar lavage (BAL) fluid cell number and protein levels were not significantly influenced by treatment with either MP (1 mg.(kg body mass)(-1).day(-1), i.p.) or 2MEO (50 mg.(kg body mass)(-1).day(-1), i.p.). Lung fibrosis, measured histopathologically or by hydroxyproline content, was not significantly influenced by either MP or 2MEO treatment, whereas the latter agent did reduce the increment in lung dry mass. The enlargement of alveolar airspaces and the decline in lung compliance were exacerbated by MP treatment. These data suggest that bleomycin-induced pulmonary fibrosis is resistant to inhibition by concurrent treatment with either glucocorticoids or 2MEO.
Similar articles
-
Overexpression of MMP9 in macrophages attenuates pulmonary fibrosis induced by bleomycin.Int J Biochem Cell Biol. 2007;39(12):2324-38. doi: 10.1016/j.biocel.2007.06.022. Epub 2007 Jul 12. Int J Biochem Cell Biol. 2007. PMID: 17702637
-
Inhibition of bleomycin-induced pulmonary fibrosis in mice by the matrix metalloproteinase inhibitor batimastat.J Pathol. 2001 Apr;193(4):538-45. doi: 10.1002/path.826. J Pathol. 2001. PMID: 11276015
-
C-C chemokine receptor 2 (CCR2) deficiency improves bleomycin-induced pulmonary fibrosis by attenuation of both macrophage infiltration and production of macrophage-derived matrix metalloproteinases.J Pathol. 2004 Dec;204(5):594-604. doi: 10.1002/path.1667. J Pathol. 2004. PMID: 15538737
-
Role of matrix metalloproteinases in the development of airway inflammation and remodeling.Braz J Med Biol Res. 2005 Oct;38(10):1521-30. doi: 10.1590/s0100-879x2005001000009. Epub 2005 Sep 6. Braz J Med Biol Res. 2005. PMID: 16172745 Review.
-
[The advances of the drug therapy for pulmonary fibrosis].Sheng Li Ke Xue Jin Zhan. 2008 Jul;39(3):233-8. Sheng Li Ke Xue Jin Zhan. 2008. PMID: 18819492 Review. Chinese.
Cited by
-
NF-kappaB Signaling in Chronic Inflammatory Airway Disease.Biomolecules. 2015 Jun 26;5(3):1266-83. doi: 10.3390/biom5031266. Biomolecules. 2015. PMID: 26131974 Free PMC article. Review.
-
Casein Kinase 1δ/ε Inhibitor, PF670462 Attenuates the Fibrogenic Effects of Transforming Growth Factor-β in Pulmonary Fibrosis.Front Pharmacol. 2018 Jul 10;9:738. doi: 10.3389/fphar.2018.00738. eCollection 2018. Front Pharmacol. 2018. PMID: 30042678 Free PMC article.
-
Glucocorticoids activate Yes-associated protein in human vocal fold fibroblasts.Exp Cell Res. 2021 Aug 15;405(2):112681. doi: 10.1016/j.yexcr.2021.112681. Epub 2021 Jun 2. Exp Cell Res. 2021. PMID: 34087241 Free PMC article.
-
Sex steroid signaling: implications for lung diseases.Pharmacol Ther. 2015 Jun;150:94-108. doi: 10.1016/j.pharmthera.2015.01.007. Epub 2015 Jan 14. Pharmacol Ther. 2015. PMID: 25595323 Free PMC article. Review.
-
Concentration Effects of Methylprednisolone in Human Vocal Fold Fibroblast-Macrophage Co-Culture.Laryngoscope. 2023 Nov;133(11):3116-3122. doi: 10.1002/lary.30763. Epub 2023 May 29. Laryngoscope. 2023. PMID: 37246727 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical