Because interferon-gamma (IFN-γ) selectively inhibits collagen gene expression, we hypothesized that expression of IFN-γ cDNA in fibroblasts might be a useful strategy to inhibit the development of fibrosis. A replication-deficient E1-, E3- adenovirus vector encoding murine IFN-γ (AdCM VmIFNγ) was constructed. Infection of murine fibroblasts with AdCM VmIFNα in vitro was well tolerated. The results showed that IN F-γ mRNA was expressed in infected cells, and as much as 17.7 ng of mIFN-γ/106 cells was secreted into culture supernatants. Steady-state levels of α1(I) procollagen mRNA were decreased by 90% in infected cells compared to uninfected cells. The inhibition of collagen mRNA expression was partially abrogated with a neutralizing anti-mIFN-γ antibody. Secretion of total collagen by AdCM VmIFVγ-infected fibroblasts was decreased by 60% compared to uninfected cells. Induction cells. Induction of cytokine responsive gene-2 expression in AdCM VmIFNγ-infected cells demonstrated that suppression of collagen production was a selective response. The results suggest a novel strategy of cytokine gene transfer and expression for the treatment of fibrotic lung diseases.
ASJC Scopus subject areas
- Molecular Biology
- Pulmonary and Respiratory Medicine
- Clinical Biochemistry