This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Siegmund, D. Articles by Wajant, H. Search for Related Content PubMed PubMed Citation Articles by Siegmund, D. Articles by Wajant, H.

Death Receptor-Induced Signaling Pathways Are Differentially Regulated by Gamma Interferon Upstream of Caspase 8 Processing

Department of Molecular Internal Medicine, Medical Polyclinic, University of Würzburg, Röntgenring 11, 97070 Würzburg, Germany,¹ Institute of Molecular Medicine, University of Düsseldorf, Universitäts-Str. 1, 40225 Düsseldorf, Germany,² Institute of Cell Biology and Immunology, University of Stuttgart, Allmandring 31, 70569 Stuttgart, Germany,³ Laboratory for Experimental Dermatology, Otto-von-Guericke-University Magdeburg, Leipzigerstr. 44, 39120 Magdeburg, Germany,⁴ Institute of Pharmacology, Medical School Hannover, Carl-Neuberg Strasse 1, 30625 Hannover, Germany⁵

Received 25 January 2005/ Returned for modification 22 February 2005/ Accepted 4 May 2005

FasL and gamma interferon (IFN-) are produced by activated T cells and NK cells and synergistically induce apoptosis. Although both cytokines can also elicit proinflammatory responses, a possible cross talk of these ligands with respect to nonapoptotic signaling has been poorly addressed. Here, we show that IFN- sensitizes KB cells for apoptosis induction by facilitating death-inducing signaling complex (DISC)-mediated caspase 8 processing. Moreover, after protection against death receptor-induced apoptosis by caspase inhibition or Bcl2 overexpression, IFN- also sensitized for Fas- and TRAIL death receptor-mediated NF-B activation leading to synergistic upregulation of a variety of proinflammatory genes. In contrast, Fas-mediated activation of JNK, p38, and p42/44 occurred essentially independent from IFN- sensitization, indicating that the apoptosis- and NF-B-related FasL-IFN- cross talk was not due to a simple global enhancement of Fas signaling. Overexpression of FLIP_L and FLIP_S inhibited Fas- as well as TRAIL-mediated NF-B activation and apoptosis induction in IFN--primed cells suggesting that both responses are coregulated at the level of the DISC.

This article has been cited by other articles:

• Greeneltch, K. M., Schneider, M., Steinberg, S. M., Liewehr, D. J., Stewart, T. J., Liu, K., Abrams, S. I. (2007). Host Immunosurveillance Controls Tumor Growth via IFN Regulatory Factor-8 Dependent Mechanisms. Cancer Res. 67: 10406-10416 [Abstract] [Full Text]  
• Kilinc, M. O., Aulakh, K. S., Nair, R. E., Jones, S. A., Alard, P., Kosiewicz, M. M., Egilmez, N. K. (2006). Reversing Tumor Immune Suppression with Intratumoral IL-12: Activation of Tumor-Associated T Effector/Memory Cells, Induction of T Suppressor Apoptosis, and Infiltration of CD8+ T Effectors. J. Immunol. 177: 6962-6973 [Abstract] [Full Text]