[Gene expression of messenger RNA coding for procollagen and tumour necrosis factor-alpha in lungs undergoing bleomycin-induced pulmonary fibrosis].

OBJECTIVE

mRNA for tumour necrosis factor-alpha(TNF-alpha) and procollagen I [pro alpha 1(I)] and III (pro alpha 1(III) was measured in bleomycin treated mice to evaluate their roles in pulmonary fibrosis.

METHOD

30 male Wistar rats were divided into normal control group and groups treated by bleomycin on days 3, 7, 14, 21, 30. Each group included 5 rats, and the rats were treated by single intratracheal instillation with sterile saline solution or with 5 mg/kg body weight of bleomycin. The rats were sacrificed at different days, and total RNA from the lungs of bleomycin or saline solution instilled rats was extracted. Expression of TNF-alpha, pro alpha 1 (I) and pro alpha 1 (III) mRNA was measured by dot blot and Northern blot hybridization.

RESULT

The levels of TNF-alpha mRNA in lungs of bleomycin groups on days 3,7 were significantly higher than those of control group (t = 10.33 and 12.54 respectively; P < 0.01). The levels of pro alpha 1 (I) and pro alpha 1(III) mRNA in lungs of bleomycin group on day 7 were higher than those of control group(t = 10.56 and 24.23 respectively; P < 0.01), After reaching the peak levels in two weeks, the levels of pro alpha 1(III) mRNA in lungs of bleomycin group on day 30 declined slowly to approximately the values of normal control group (t = 1.95; P > 0.05); but the levels of pro alpha 1(I) mRAN on day 30 after bleomycin administration were higher than those of control group (t = 16.67; P < 0.01). The mRNA coding pro alpha 1(I) and pro alpha 1(III) in lungs of rats had two mRNA species.

CONCLUSION

The results suggested that the metabolism of mRNAs for pro alpha 1 (I) and pro alpha 1 (III) may be preferentially perturbed, and that increase of collagen gene expression in the transcriptional level might be involved in the mechanism of collagen accumulation. The increased expression of TNF-alpha gene may play an important role in the early events of bleomycin-induced pulmonary fibrosis.