These histopathologic changes induced by the transforming growth factor beta 1 and platelet-derived growth factor B gene are partly akin to those changes seen in lung tissues from patients with pulmonary fibrosis and markedly contrast with the changes induced by overexpression of the IL-6 and IL-6 receptor genes that mimics lymphocytic interstitial pneumonia.
We conclude that a decreased capacity to up-regulate COX-2 expression and COX-2-derived PGE(2) synthesis in the presence of increasing levels of profibrotic mediators such as TGF-beta(1) may lead to unopposed fibroblast proliferation and collagen synthesis and contribute to the pathogenesis of pulmonary fibrosis.
The results indicate a role for induction of c-jun and TGF-beta 1 expression in the development of AM-induced pulmonary fibrosis in the Fischer 344 rat and provide potential targets for therapeutic intervention.
Two anti-inflammatory cytokines, interleukin-1 receptor antagonist and transforming growth factor-beta1, had increased expression, consistent with other human fibrotic lung diseases and animal models of lung fibrosis.
These findings suggest that the differences in susceptibility to pulmonary fibrosis are downstream from TGF-beta1 and that fibrosis-prone individuals may have an altered collagen metabolism in the lungs that is balanced toward a "nondegrading" environment.
Early elevated cutaneous mRNA expression of TGF-beta1, but not TGF-beta2 or TGF-beta3, and elevated C-C chemokines macrophage chemoattractant protein-1, macrophage inflammatory protein-1alpha, and RANTES precede subsequent skin and lung fibrosis.
Our results indicate that the homozygous wild type of the G915C single nucleotide polymorphism in the coding region of the TGF-beta1 gene, which was recently associated with elevated TGF-beta1 production and pulmonary fibrosis, may influence the predisposition to Peyronie's disease.
Our results suggest that TGFbeta1 polymorphisms do not play a role in the pathogenesis of SSc, even though there remains the possibility of a risk factor for genetic susceptibility to pulmonary fibrosis.
In addition, profibrotic transforming growth factor-beta1 (TGF-beta1) was decreased in hHGF-treated lungs, indicating an involvement of TGF-beta1 in hHGF-induced reduction of lung fibrosis.
We have recently reported that IL-6 and TGF-beta(1) plays an important role in proliferation and differentiation of lung fibroblasts, and all-trans-retinoic acid (ATRA) prevented bleomycin-induced lung fibrosis through the inhibition of these cytokines.
Because the transcriptional response of fibroblasts to transforming growth factor-beta(1) (TGF-beta(1)) is a determinant of disease progression, we investigated the role of the transcriptional regulator inhibitor of differentiation-1 (Id1) in the setting of lung fibrosis.
TGF-beta1-induced upregulation of arginase-1 suggests an interplay between profibrotic agents and l-arginine metabolism during the course of lung fibrosis in the mouse, whereas species-specific regulatory mechanisms may account for the differences observed in mouse and human.
Mediators of preferably mesenchymal repair such as transforming growth factor beta(1) (TGF-beta(1)) and mediators of polarized cellular immunity such as interleukin (IL)-13 are thought to be of key importance for progression of lung fibrosis.
To investigate the association between TGF-beta1 gene polymorphisms in codons 10 and 25 and the susceptibility to asbestos-induced diseases, association studies were performed with healthy control subjects (n = 83), patients with pulmonary fibrosis (n = 591), and patients with bronchial carcinoma (n = 147).
In vitro studies disclosed that Calpeptin reduced (i) production of IL-6, TGF-β1, angiopoietin-1 and collagen synthesis from lung fibroblasts; and (ii) both IL-6-dependent proliferation and angiopoietin-1-dependent migration of the cells, which could be the mechanism underlying the preventive effect of Calpeptin on pulmonary fibrosis.
Transforming growth factor-β1 (TGF-β1, a potent profibrotic cytokine) and plasminogen activator inhibitor 1 (PAI-1) play important roles in the development of pulmonary fibrosis.