Idiopathic pulmonary fibrosis (IPF) is a poorly understood immunomediated dis- -jer: in the past few years interest in the pathogenetic mechanisms taking place i IPF has focused on immune effector cells that are involved in pulmonary • 'immatory pathways, cell-specific injury, and fibroblast activation. In particular, a. cumulating evidence indicates that a complex relationship exists between the jcrophage/lymphocyte/neutrophil cellular axis and the local network of cytokines fciL through paracrine and autocrine interactions, coordinate inflammation and - 'cogenesis in the respiratory tract. We determined levels of two potentially important mediators of fibroproliferative ~:7air in BAL fluid from patients with lung fibrosis. Methods: Using Western blot and ELISA techniques we measured levels of platelet :enved growth factor (PDGF) and transforming growth factor-beta (TGF-/J) in E \L fluid from patients with IPF and healthy controls. The mitogenic effect of these cytokines on lung fibroblats was determined by [3H]thymidine incorporation. Results: IPF BAL fluid contains significantly elevated levels of PDGF-AA and PDGF-BB. Where TGF-/U was significantly elevated in IPF lavage fluid, the amount of TGF-/22 was significantly less than that observed in normal lavage fluid. Fibroblasts cultured from IPF lavage fluid exhibited enhanced [3 H] thymidine in¬corporation upon exposure to the growth factors present in IPF BAL fluid: PDGF and TGF-/31. Lung fibroblasts pretreated with TGF-/31 exhibited an enhanced mitogenic effect upon stimulation by PDGF, due in part to the induction of the PDGF a, receptor. Conclusion: Our studies support a role for PDGF and TGF-fi 1 in the pathogenesis of IPF lung disease.

FIBROBLAST PROLIFERATION INDUCED BY GROWTH FACTORS IN DIOPATHIC PULMONARY FIBROSIS

MAZZARELLA, Gennaro;CALABRESE, Cecilia;
1998

Abstract

Idiopathic pulmonary fibrosis (IPF) is a poorly understood immunomediated dis- -jer: in the past few years interest in the pathogenetic mechanisms taking place i IPF has focused on immune effector cells that are involved in pulmonary • 'immatory pathways, cell-specific injury, and fibroblast activation. In particular, a. cumulating evidence indicates that a complex relationship exists between the jcrophage/lymphocyte/neutrophil cellular axis and the local network of cytokines fciL through paracrine and autocrine interactions, coordinate inflammation and - 'cogenesis in the respiratory tract. We determined levels of two potentially important mediators of fibroproliferative ~:7air in BAL fluid from patients with lung fibrosis. Methods: Using Western blot and ELISA techniques we measured levels of platelet :enved growth factor (PDGF) and transforming growth factor-beta (TGF-/J) in E \L fluid from patients with IPF and healthy controls. The mitogenic effect of these cytokines on lung fibroblats was determined by [3H]thymidine incorporation. Results: IPF BAL fluid contains significantly elevated levels of PDGF-AA and PDGF-BB. Where TGF-/U was significantly elevated in IPF lavage fluid, the amount of TGF-/22 was significantly less than that observed in normal lavage fluid. Fibroblasts cultured from IPF lavage fluid exhibited enhanced [3 H] thymidine in¬corporation upon exposure to the growth factors present in IPF BAL fluid: PDGF and TGF-/31. Lung fibroblasts pretreated with TGF-/31 exhibited an enhanced mitogenic effect upon stimulation by PDGF, due in part to the induction of the PDGF a, receptor. Conclusion: Our studies support a role for PDGF and TGF-fi 1 in the pathogenesis of IPF lung disease.
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11591/217784
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus ND
  • ???jsp.display-item.citation.isi??? ND
social impact