title: Dual role of TGF-β1 on Fas-induced apoptosis in lung epithelial cells.
abstract: Recent evidence suggests that TGF-β1 has a dual role in regulating cell response to Fas/Fas ligand (FasL)-induced apoptosis. TGF-β1 may play a positive or negative role on cell sensitivity to apoptosis via Fas/FasL system, depending on cell types and their specific environment. TGF-β1 and the Fas/FasL system are also involved in pathological processes of acute lung injury (ALI) and interstitial lung diseases including early lung injury and subsequent tissue repair. However, it is not well understood how TGF-β1 regulates Fas/FasL mediated apoptotic signaling in lung epithelium. In this study, we found that TGF-β1 could affect the sensitivity of lung epithelial A549 cells to Fas/FasL mediated apoptosis in a time-dependent manner. Apoptosis of A549 cells could be enhanced significantly by co-treatment with TGF-β1 and FasL, or pretreatment with TGF-β1 followed by FasL exposure, as evidenced by markedly increased caspase-8 and JNK activities. However, prolonged exposure to TGF-β1 could result in an obvious inhibition of the Fas/FasL-induced apoptosis, accompanied by down-regulation of Fas and up-regulation of c-Flip. Our results also showed that the effect of TGF-β1 on cell sensitivity to Fas-mediated apoptosis was independent of Akt pathway activation. These findings suggest that timely interplay of TGF-β1 and the Fas/FasL system could determine the final outcomes of cell survival/death signaling, for example, switching cell death signaling to survival signaling during early injury and later repair process of lung epithelium.
authors.affiliation: Institute of Respiratory Diseases, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, PR China. blpost@126.com
authors.forename: Li
authors.initials: L
authors.lastname: Bai
authors.forename: Zubin
authors.initials: Z
authors.lastname: Yu
authors.forename: Changzheng
authors.initials: C
authors.lastname: Wang
authors.forename: Guisheng
authors.initials: G
authors.lastname: Qian
authors.forename: Guansong
authors.initials: G
authors.lastname: Wang
mesh_terms: D000704:Analysis of Variance; D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D053181:Caspase 8 / Q000378:metabolism; D002461:Cell Line, Transformed; D004347:Drug Interactions; D004847:Epithelial Cells / Q000187:drug effects*; D053222:Fas Ligand Protein / Q000494:pharmacology*; D006801:Humans; D008168:Lung / Q000166:cytology*; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D011419:Propidium; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*
chemical_list: D017304:Annexin A5; D053222:Fas Ligand Protein; D053773:Transforming Growth Factor beta1; D011419:Propidium; D048670:MAP Kinase Kinase 4; D053181:Caspase 8