The central role of Fas-ligand cell signaling in inflammatory lung diseases.
Following inflammation and injury in the lung, loss of epithelial cell precursors could determine the balance between tissue regeneration and fibrosis. This review discusses evidence that proapoptotic Fas-Fas ligand (FasL) signaling plays a central role in pulmonary inflammation, injury and fibrosis. FasL signaling induces inflammatory apoptosis in epithelial cells and alveolar macrophages, with concomitant IL-1 beta and chemokine release, leading to neutrophil infiltration. FasL signaling plays a critical role in models of acute lung injury, idiopathic pulmonary fibrosis and silicosis; blockade of Fas-FasL interactions either prevents or attenuates pulmonary inflammation and fibrosis. Serologic and immunohistochemical studies in patients support a major pathogenic role of Fas and FasL molecules in inflammatory lung diseases. Identification of the pathogenic role of FasL could facilitate the discovery of more effective treatments for currently untreatable inflammatory lung diseases.
Dosreis
G A
GA
Instituto de Biofísica Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, RJ 21949-900, Brazil. gdosreis@biof.ufrj.br
Borges
Valeria M
VM
Zin
W A
WA
D000208:Acute Disease; D017209:Apoptosis; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D053222:Fas Ligand Protein; D005786:Gene Expression Regulation; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000276:immunology / Q000473:pathology; D008562:Membrane Glycoproteins / Q000502:physiology*; D009504:Neutrophils / Q000276:immunology; D011014:Pneumonia / Q000276:immunology* / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000276:immunology / Q000378:metabolism; D011658:Pulmonary Fibrosis / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction; D012829:Silicosis / Q000276:immunology; D019014:fas Receptor / Q000276:immunology*
C505661:FASLG protein, human; D053222:Fas Ligand Protein; D007375:Interleukin-1; D008562:Membrane Glycoproteins; D019014:fas Receptor