Opposing effect by cytokines on Fas-mediated apoptosis in A549 lung epithelial cells

K. R. Coulter, A. Doseff, P. Sweeney, Y. Wang, C. B. Marsh, M. D. Wewers, Daren L Knoell

Research output: Contribution to journalArticle

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Abstract

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) -γ and interleukin (IL)-1β have opposing effects on Fas-mediated apoptosis in A549 cells, a human lung epithelial cell line. Exposure to IFN-γ 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-γ was 3-fold higher than with Fas activation alone. In contrast, pretreatment with IL-1β before Fas activation completely inhibited apoptosis. Furthermore, our results demonstrate that IFN-γ and IL-1β induce opposite effects at multiple checkpoints during Fas-mediated apoptosis. Most striking, IL-1β 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-1β and IFN-γ on Fas-mediated apoptosis are in part dependent on modulation of the PI 3-K/Akt survival pathway.

Original languageEnglish (US)
Pages (from-to)58-66
Number of pages9
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume26
Issue number1
DOIs
StatePublished - Jan 1 2002

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Interleukin-1
Interferons
Epithelial Cells
Apoptosis
Cytokines
Chemical activation
Lung
Caspases
Cytoskeletal Proteins
Caspase 8
Repair
Modulation
Tissue
Inflammation
Cell Line
Survival
Processing

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

Cite this

Opposing effect by cytokines on Fas-mediated apoptosis in A549 lung epithelial cells. / Coulter, K. R.; Doseff, A.; Sweeney, P.; Wang, Y.; Marsh, C. B.; Wewers, M. D.; Knoell, Daren L.

In: American Journal of Respiratory Cell and Molecular Biology, Vol. 26, No. 1, 01.01.2002, p. 58-66.

Research output: Contribution to journalArticle

Coulter, K. R. ; Doseff, A. ; Sweeney, P. ; Wang, Y. ; Marsh, C. B. ; Wewers, M. D. ; Knoell, Daren L. / Opposing effect by cytokines on Fas-mediated apoptosis in A549 lung epithelial cells. In: American Journal of Respiratory Cell and Molecular Biology. 2002 ; Vol. 26, No. 1. pp. 58-66.
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