Am. J. Respir. Cell Mol. Biol., Volume 26, Number 1, January, 2002 58-66

Opposing Effect by Cytokines on Fas-Mediated Apoptosis in A549 Lung Epithelial Cells

Kristin R. Coulter, Andrea Doseff, Patricia Sweeney, Yijie Wang, Clay B. Marsh, Mark D. Wewers, and Daren L. Knoell

Department of Pharmacy, Ohio State University College of Pharmacy, and Department of Internal Medicine, Ohio State University College of Medicine, Columbus, Ohio

Tissue repair is determined by many signals provided in the local environment. Central to this process is the commitment of the parenchymal cell to undergo apoptosis, survive, or proliferate following inflammation. We hypothesize that lung epithelial cell apoptosis is influenced by exposure to cytokines released into the alveolar microenvironment during the inflammatory process. In this investigation we demonstrate that interferon (IFN)- and interleukin (IL)-1 have opposing effects on Fas-mediated apoptosis in A549 cells, a human lung epithelial cell line. Exposure to IFN- before Fas activation significantly increased caspase activity, caspase processing of CK-18, a key cytoskeletal protein in epithelial cells, and increased the appearance of apoptotic nuclei. Induction of Fas-mediated death by IFN- was 3-fold higher than with Fas activation alone. In contrast, pretreatment with IL-1 before Fas activation completely inhibited apoptosis. Furthermore, our results demonstrate that IFN- and IL-1 induce opposite effects at multiple checkpoints during Fas-mediated apoptosis. Most striking, IL-1 prevented the activation of caspases involved in Fas-mediated death by inducing an anti-apoptotic effect proximal to or at the point of caspase-8 activation. Finally, our investigation demonstrates that the differential impact of IL-1 and IFN- on Fas-mediated apoptosis are in part dependent on modulation of the PI 3-K/Akt survival pathway.

This article has been cited by other articles:

				B. Besecker, S. Bao, B. Bohacova, A. Papp, W. Sadee, and D. L. Knoell The human zinc transporter SLC39A8 (Zip8) is critical in zinc-mediated cytoprotection in lung epithelia Am J Physiol Lung Cell Mol Physiol, June 1, 2008; 294(6): L1127 - L1136. [Abstract] [Full Text] [PDF]

				G. M. Albaiceta, A. Gutierrez-Fernandez, D. Parra, A. Astudillo, E. Garcia-Prieto, F. Taboada, and A. Fueyo Lack of matrix metalloproteinase-9 worsens ventilator-induced lung injury Am J Physiol Lung Cell Mol Physiol, March 1, 2008; 294(3): L535 - L543. [Abstract] [Full Text] [PDF]

				C. Quesnel, S. Marchand-Adam, A. Fabre, J. Marchal-Somme, I. Philip, S. Lasocki, V. Lecon, B. Crestani, and M. Dehoux Regulation of hepatocyte growth factor secretion by fibroblasts in patients with acute lung injury Am J Physiol Lung Cell Mol Physiol, February 1, 2008; 294(2): L334 - L343. [Abstract] [Full Text] [PDF]

				S. Bao and D. L. Knoell Zinc modulates cytokine-induced lung epithelial cell barrier permeability Am J Physiol Lung Cell Mol Physiol, December 1, 2006; 291(6): L1132 - L1141. [Abstract] [Full Text] [PDF]

				Y. Tesfaigzi Roles of Apoptosis in Airway Epithelia Am. J. Respir. Cell Mol. Biol., May 1, 2006; 34(5): 537 - 547. [Abstract] [Full Text] [PDF]

				S. Bao and D. L. Knoell Zinc modulates airway epithelium susceptibility to death receptor-mediated apoptosis Am J Physiol Lung Cell Mol Physiol, March 1, 2006; 290(3): L433 - L441. [Abstract] [Full Text] [PDF]

				C. L. Speyer, N. J. Rancilio, S. D. McClintock, J. D. Crawford, H. Gao, J. V. Sarma, and P. A. Ward Regulatory effects of estrogen on acute lung inflammation in mice Am J Physiol Cell Physiol, April 1, 2005; 288(4): C881 - C890. [Abstract] [Full Text] [PDF]

				S. Bao, Y. Wang, P. Sweeney, A. Chaudhuri, A. I. Doseff, C. B. Marsh, and D. L. Knoell Keratinocyte growth factor induces Akt kinase activity and inhibits Fas-mediated apoptosis in A549 lung epithelial cells Am J Physiol Lung Cell Mol Physiol, January 1, 2005; 288(1): L36 - L42. [Abstract] [Full Text] [PDF]

				T. M. O'Connor and C. P. Bredin Interferon-{gamma} Toxicity in Idiopathic Pulmonary Fibrosis Am. J. Respir. Crit. Care Med., February 1, 2004; 169(3): 428 - 428. [Full Text]

				P. Linscheid, D. Seboek, E. S. Nylen, I. Langer, M. Schlatter, K. L. Becker, U. Keller, and B. Muller In Vitro and in Vivo Calcitonin I Gene Expression in Parenchymal Cells: A Novel Product of Human Adipose Tissue Endocrinology, December 1, 2003; 144(12): 5578 - 5584. [Abstract] [Full Text] [PDF]

				M. J. Segel, G. Izbicki, P. Y. Cohen, R. Or, T. G. Christensen, S. B. Wallach-Dayan, and R. Breuer Role of interferon-{gamma} in the evolution of murine bleomycin lung fibrosis Am J Physiol Lung Cell Mol Physiol, December 1, 2003; 285(6): L1255 - L1262. [Abstract] [Full Text] [PDF]