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

J. Biol. Chem., Vol. 283, Issue 37, 25132-25139, September 12, 2008

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 283/37/25132    most recent M804770200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Chakrabarti, A. Articles by Williams, B. R. G. Search for Related Content PubMed PubMed Citation Articles by Chakrabarti, A. Articles by Williams, B. R. G. Social Bookmarking                      What's this?

Protein Kinase R-dependent Regulation of Interleukin-10 in Response to Double-stranded RNA^*

Arindam Chakrabarti¹, Anthony J. Sadler¹, Niladri Kar^¶, Howard A. Young^||, Robert H. Silverman, and Bryan R. G. Williams²

From the Departments of Cancer Biology and ^¶Molecular Cardiology, Lerner Research Institute, The Cleveland Clinic, Cleveland, Ohio 44195, the Monash Institute of Medical Research, Monash University, Clayton, Victoria 3168, Australia, and the ^||Laboratory of Experimental Immunology, NCI-Frederick, National Institutes of Health, Frederick, Maryland 21702

The double-stranded RNA-activated protein kinase R (PKR) is an important component of antiviral defense. PKR participates in different signaling pathways in response to various stimuli to regulate translation via phosphorylation of the eukaryotic initiation factor 2, and transcription via activating NF-B and IRF-1, to induce pro-inflammatory cytokines. Here we show PKR regulates interleukin-10 induction in response to double-stranded RNA, bacterial lipopolysaccaride, and Sendai virus infection. Using chemical inhibitors, dominant negative constructs, and genetic knockouts, we demonstrate that the PKR-mediated interleukin-10 induction engages JNK and NF-B. Together, our data demonstrate the role of PKR in regulating an anti-inflammatory cytokine. The findings have significance in antiviral as well as broader innate immune responses.

Received for publication, June 23, 2008 , and in revised form, July 7, 2008.

^* This work was supported, in whole or in part, by National Institutes of Health Grants R01 AI034039 and P01 CA062220. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Figs. S1–S4.

¹ Both authors contributed equally to this work.

² To whom correspondence should be addressed: Monash Institute of Medical Research, Monash Medical Centre, 246 Clayton Rd, Clayton, Victoria 3168, Australia. Tel.: 61-3-9594-7166; Fax: 61-3-9594-7167; E-mail: bryan.williams{at}med.monash.edu.au.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				C. Myskiw, J. Arsenio, R. van Bruggen, Y. Deschambault, and J. Cao Vaccinia Virus E3 Suppresses Expression of Diverse Cytokines through Inhibition of the PKR, NF-{kappa}B, and IRF3 Pathways J. Virol., July 1, 2009; 83(13): 6757 - 6768. [Abstract] [Full Text] [PDF]

				R. Norden, K. Nystrom, and S. Olofsson Activation of host antiviral RNA-sensing factors necessary for herpes simplex virus type 1-activated transcription of host cell fucosyltransferase genes FUT3, FUT5, and FUT6 and subsequent expression of sLex in virus-infected cells Glycobiology, July 1, 2009; 19(7): 776 - 788. [Abstract] [Full Text] [PDF]