Molecular mechanisms of antifibrotic effect of interferon gamma in bleomycin-mouse model of lung fibrosis: Downregulation of TGF-{beta} and procollagen I and III gene expression

Journal Article · Sun Dec 31 04:00:00 EST 1995 · Experimental Lung Research

DOI:https://doi.org/10.3109/01902149509050842· OSTI ID:525995

Gurujeyalakshmi, G; Giri, S N ^[1]

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1. Univ. of California, Davis, CA (United States)

The present study was undertaken to elucidate the mechanism for the antifibrotic effect of interferon gamma (IFN-{gamma}) in the bleomycin (BL)-mouse model of lung fibrosis. The expression of transforming growth factor (TGF-{beta}) and procollagen I and III and their mRNAs was investigated in the BL-mouse model of lung fibrosis with and without IFN-{gamma} treatment by Northern and slot blot analyses. Temporal changes in the content of procollagen and TGF-{beta} mRNAs in the lungs of mice receiving saline or BL by intratracheal route, with and without IFN-{gamma} treatment by intramuscular route, were quantitated. The level of TGF-{beta} mRNA increased rapidly and peaked at day 5, whereas the levels of mRNAs for procollagens {alpha}{sub 1}(I) and {alpha}{sub 1}(III) peaked at 10 days after BL instillation. The peak levels of these mRNAs in BL-treated animals were five- to seven-fold higher than those of the control. BL treatment also increased the hydroxyproline content significantly from 3 to 14 days as compared to the corresponding saline control groups. A maximal increase to 447 {mu}g/lung from 223 {mu}g/lung in saline control was obtained at 10 days after instillation. Daily treatment with IFN-{gamma} markedly reduced the BL-induced increases in the mRNA levels of TGF-{beta}, and procollagen {alpha}{sub 1}(I) and {alpha}{sub 1}(III) without any effect on the lung level of {beta}-actin mRNA. IFN-{gamma} treatment also caused significant reduction in the BL-induced increase in the lung hydroxyproline content from 417 to 283 {mu}g/lung at 7 days and from 447 to 264 {mu}g/lung at 10 days. It may be concluded from the findings of the present study that the cellular mechanisms for the antifibrotic effect of IFN-{gamma} in the BL-mouse model of lung fibrosis are to initially downregulate the BL-induced overexpression of TFG-{beta} mRNA, and subsequently procollagen mRNAs, leading to a decreased collagen content. 42 refs., 7 figs.

• Sponsoring Organization: USDOE
• OSTI ID: 525995
• Journal Information: Experimental Lung Research, Journal Name: Experimental Lung Research Journal Issue: 5 Vol. 21; ISSN 0190-2148; ISSN EXLRDA
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
BIOLOGICAL EFFECTS
BIOLOGICAL MODELS
BLEOMYCIN
COLLAGEN
DNA HYBRIDIZATION
FIBROSIS
GENE REGULATION
INTERFERON
LUNGS
MESSENGER-RNA
MICE
PATHOGENESIS
TRANSCRIPTION FACTORS