Am. J. Respir. Cell Mol. Biol., Volume 18, Number 3, March, 1998 334-342

Regulation of Transforming Growth Factor-₁ mRNA Expression by Taurine and Niacin in the Bleomycin Hamster Model of Lung Fibrosis

G. Gurujeyalakshmi, M. A. Hollinger, and S. N. Giri

Department of Molecular Biosciences, School of Veterinary Medicine; and Department of Pharmacology and Toxicology, School of Medicine, University of California, Davis, California

We have reported that taurine (T) and niacin (N) inhibit the expression of procollagen type I and type III genes at the level of gene transcription in the bleomycin (BL) hamster model of lung fibrosis. In the present study, we have investigated the effects of TN in diet on the temporal expression of transforming growth factor-₁ (TGF-₁) mRNA and TGF-₁ protein production in the same model of lung fibrosis to determine whether the decreased transcription of procollagen genes is associated with downregulation of TGF-₁ mRNA. Our results demonstrate that expression of TGF-₁ mRNA in lungs is increased in BL-treated hamsters in the BL + control diet (CD) group, compared to saline controls in the saline-instilled (SA) + CD group, by 3.5-, 2.5-, 4-, and 2-fold at 3, 7, 14, and 21 d, respectively, and TN treatment caused significant decreases in TGF-₁ mRNA expression in BL-treated animals in the BL + TN group from Day 3 through Day 21. In addition, TN treatment also reduced TGF-₁ protein in bronchoalveolar lavage fluid (BALF) from BL-treated animals in the BL + TN group. These decreases in TGF-₁ mRNA and TGF-₁ protein correlated with decreased lung collagen content in hamsters in the BL + TN group as demonstrated in our earlier study. To confirm that the TGF-₁ activity observed in BALF is reflected at the transcriptional level, total RNA was isolated from lavaged cells. Reverse transcriptase-polymerase chain reaction analysis demonstrated maximal expression of TGF-₁ mRNA transcripts in BL-treated lavaged cells from animals in the BL + CD group and only low levels were detected in both saline control groups, and in BL + TN-treated lavaged cells. Nuclear runoff analysis indicated that TN-mediated reduction of TGF-₁ mRNA steady-state levels was a result of decreased gene transcription, suggesting a transcriptional downregulation mechanism. Our results indicate that the combined treatment with TN ameliorates BL-induced lung fibrosis, at least in part, via inhibition of TGF-₁ mRNA expression.

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