HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Takahashi, K. Articles by Akira, S. Search for Related Content PubMed PubMed Citation Articles by Takahashi, K. Articles by Akira, S.

Cutting Edge: Roles of Caspase-8 and Caspase-10 in Innate Immune Responses to Double-Stranded RNA

Ken Takahashi^*,, Taro Kawai, Himanshu Kumar^*, Shintaro Sato, Shin Yonehara and Shizuo Akira^1,*,

^* Department of Host Defense and Exploratory Research for Advanced Technology, Japan Science and Technology Agency, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan; and Department of Gastroenterology and Hepatology, Graduate School of Medicine and Graduate School of Biostudies, Kyoto University, Kyoto, Japan

Upon viral infection, host cells trigger antiviral immune responses by inducing type I IFN and inflammatory cytokines. dsRNA generated during viral replication is recognized by the cytoplasmic RNA helicases retinoic acid-inducible gene I and melanoma differentiation-associated gene 5, which interact with an adaptor, IFN- promoter stimulator-1, to activate the transcription factors NF-B and IFN regulatory factor 3. In this article we demonstrate that caspase-8 and caspase-10 are involved in these pathways. Both caspases were cleaved during dsRNA stimulation, and overexpression of a cleaved form of these caspases activated NF-B. Knockdown of caspase-10 or caspase-8 in a human cell line resulted in the reduction of inflammatory cytokine production. Cells derived from caspase-8-deficient mice also showed reduced expression of inflammatory cytokines as well as NF-B activation. Furthermore, the Fas-associated death domain protein interacted with these two caspases and IFN- promoter stimulator 1. These results indicate that caspase-8 and caspase-10 are essential components that mediate NF-B-dependent inflammatory responses in antiviral signaling.

This article has been cited by other articles:

				R. E. Randall and S. Goodbourn Interferons and viruses: an interplay between induction, signalling, antiviral responses and virus countermeasures J. Gen. Virol., January 1, 2008; 89(1): 1 - 47. [Abstract] [Full Text] [PDF]

				U. Lakshmanan and A. G. Porter Caspase-4 Interacts with TNF Receptor-Associated Factor 6 and Mediates Lipopolysaccharide-Induced NF-{kappa}B-Dependent Production of IL-8 and CC Chemokine Ligand 4 (Macrophage-Inflammatory Protein-1 ) J. Immunol., December 15, 2007; 179(12): 8480 - 8490. [Abstract] [Full Text] [PDF]

				T. Venkataraman, M. Valdes, R. Elsby, S. Kakuta, G. Caceres, S. Saijo, Y. Iwakura, and G. N. Barber Loss of DExD/H Box RNA Helicase LGP2 Manifests Disparate Antiviral Responses J. Immunol., May 15, 2007; 178(10): 6444 - 6455. [Abstract] [Full Text] [PDF]

				S. Balachandran, T. Venkataraman, P. B. Fisher, and G. N. Barber Fas-Associated Death Domain-Containing Protein-Mediated Antiviral Innate Immune Signaling Involves the Regulation of Irf7 J. Immunol., February 15, 2007; 178(4): 2429 - 2439. [Abstract] [Full Text] [PDF]

				T. Kawai and S. Akira Antiviral Signaling Through Pattern Recognition Receptors J. Biochem., February 1, 2007; 141(2): 137 - 145. [Abstract] [Full Text] [PDF]

				H. Kumar, T. Kawai, H. Kato, S. Sato, K. Takahashi, C. Coban, M. Yamamoto, S. Uematsu, K. J. Ishii, O. Takeuchi, et al. Essential role of IPS-1 in innate immune responses against RNA viruses J. Exp. Med., July 10, 2006; 203(7): 1795 - 1803. [Abstract] [Full Text] [PDF]