Protein kinase R-dependent regulation of interleukin-10 in response to double-stranded RNA

Arindam Chakrabarti, Anthony John Sadler, Niladri Kar, Howard A Young, Robert H Silverman, Bryan Raymond George Williams

Research output: Contribution to journalArticleResearchpeer-review

31 Citations (Scopus)

Abstract

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 2alpha, and transcription via activating NF-kappaB 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-kappaB. 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.
Original languageEnglish
Pages (from-to)25132 - 25139
Number of pages8
JournalThe Journal of Biological Chemistry
Volume283
Issue number37
Publication statusPublished - 2008

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