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- Publisher Website: 10.1093/toxsci/kfn128
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- PMID: 18599499
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Article: Double-stranded RNA - Activated protein kinase mediates induction of interleukin-8 expression by deoxynivalenol, shiga toxin 1, and ricin in monocytes
Title | Double-stranded RNA - Activated protein kinase mediates induction of interleukin-8 expression by deoxynivalenol, shiga toxin 1, and ricin in monocytes | ||||
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Authors | |||||
Keywords | Immunotoxicity Kinase Ribotoxic stress chemokine | ||||
Issue Date | 2008 | ||||
Publisher | Oxford University Press. The Journal's web site is located at http://toxsci.oxfordjournals.org/ | ||||
Citation | Toxicological Sciences, 2008, v. 105 n. 2, p. 322-330 How to Cite? | ||||
Abstract | Translational inhibitors such as the trichothecene mycotoxin deoxynivalenol (DON) and ribosomal inhibitory proteins (RIPs) induce mitogen-activated protein kinase (MAPK)-driven chemokine and cytokine production by a mechanism known as the ribotoxic stress response (RSR). Double-stranded RNA-activated protein kinase (PKR) associates with the ribosome making it uniquely positioned to sense 28S ribosomal RNA damage and initiate the RSR. We have previously shown that PKR mediates DON-induced MAPK phosphorylation in macrophages and monocytes. The purpose of this study was to test the hypothesis that PKR is essential for induction of interleukin (IL)-8 expression in monocytes by DON and two prototypical RIPs, ricin, and Shiga toxin 1 (Stx1). Preincubation of human monocytic U937 cells with the PKR inhibitors C16 and 2-aminopurine (2-AP) blocked DON-induced expression of IL-8 protein and mRNA. Induction of IL-8 expression was similarly impaired in U937 cells stably transfected with a dominant negative PKR plasmid (UK9M) as compared with cells transfected with control plasmid (UK9C). Nuclear factor-kappa B binding, which has been previously shown to be a requisite for DON-induced IL-8 transcription, was markedly reduced in UK9M cells as compared with UK9C cells. As observed for DON, ricin-, and Stx1-induced IL-8 expression was suppressed by the PKR inhibitors C16 and 2-AP as well as impaired in UK9M cells. Taken together, these data indicate that PKR plays a common role in IL-8 induction by DON and the two RIPs, suggesting that this kinase might be a critical factor in RSR. © The Author 2008. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. | ||||
Persistent Identifier | http://hdl.handle.net/10722/80064 | ||||
ISSN | 2023 Impact Factor: 3.4 2023 SCImago Journal Rankings: 0.911 | ||||
PubMed Central ID | |||||
ISI Accession Number ID |
Funding Information: Public Health Service Grants (ES03358 and DK58833) to J.J.P. | ||||
References |
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Gray, JS | en_HK |
dc.contributor.author | Bae, HK | en_HK |
dc.contributor.author | Li, JCB | en_HK |
dc.contributor.author | Lau, AS | en_HK |
dc.contributor.author | Pestka, JJ | en_HK |
dc.date.accessioned | 2010-09-06T08:01:57Z | - |
dc.date.available | 2010-09-06T08:01:57Z | - |
dc.date.issued | 2008 | en_HK |
dc.identifier.citation | Toxicological Sciences, 2008, v. 105 n. 2, p. 322-330 | en_HK |
dc.identifier.issn | 1096-6080 | en_HK |
dc.identifier.uri | http://hdl.handle.net/10722/80064 | - |
dc.description.abstract | Translational inhibitors such as the trichothecene mycotoxin deoxynivalenol (DON) and ribosomal inhibitory proteins (RIPs) induce mitogen-activated protein kinase (MAPK)-driven chemokine and cytokine production by a mechanism known as the ribotoxic stress response (RSR). Double-stranded RNA-activated protein kinase (PKR) associates with the ribosome making it uniquely positioned to sense 28S ribosomal RNA damage and initiate the RSR. We have previously shown that PKR mediates DON-induced MAPK phosphorylation in macrophages and monocytes. The purpose of this study was to test the hypothesis that PKR is essential for induction of interleukin (IL)-8 expression in monocytes by DON and two prototypical RIPs, ricin, and Shiga toxin 1 (Stx1). Preincubation of human monocytic U937 cells with the PKR inhibitors C16 and 2-aminopurine (2-AP) blocked DON-induced expression of IL-8 protein and mRNA. Induction of IL-8 expression was similarly impaired in U937 cells stably transfected with a dominant negative PKR plasmid (UK9M) as compared with cells transfected with control plasmid (UK9C). Nuclear factor-kappa B binding, which has been previously shown to be a requisite for DON-induced IL-8 transcription, was markedly reduced in UK9M cells as compared with UK9C cells. As observed for DON, ricin-, and Stx1-induced IL-8 expression was suppressed by the PKR inhibitors C16 and 2-AP as well as impaired in UK9M cells. Taken together, these data indicate that PKR plays a common role in IL-8 induction by DON and the two RIPs, suggesting that this kinase might be a critical factor in RSR. © The Author 2008. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. | en_HK |
dc.language | eng | en_HK |
dc.publisher | Oxford University Press. The Journal's web site is located at http://toxsci.oxfordjournals.org/ | en_HK |
dc.relation.ispartof | Toxicological Sciences | en_HK |
dc.rights | Toxicological Sciences. Copyright © Oxford University Press. | en_HK |
dc.subject | Immunotoxicity | en_HK |
dc.subject | Kinase | en_HK |
dc.subject | Ribotoxic stress chemokine | en_HK |
dc.title | Double-stranded RNA - Activated protein kinase mediates induction of interleukin-8 expression by deoxynivalenol, shiga toxin 1, and ricin in monocytes | en_HK |
dc.type | Article | en_HK |
dc.identifier.openurl | http://library.hku.hk:4550/resserv?sid=HKU:IR&issn=1096-6080&volume=105&issue=2&spage=322&epage=30&date=2008&atitle=Double-stranded+RNA-activated+protein+kinase+mediates+induction+of+interleukin-8+expression+by+deoxynivalenol,+Shiga+toxin+1,+and+ricin+in+monocytes | en_HK |
dc.identifier.email | Li, JCB: jamesli@hku.hk | en_HK |
dc.identifier.email | Lau, AS: asylau@hku.hk | en_HK |
dc.identifier.authority | Li, JCB=rp00496 | en_HK |
dc.identifier.authority | Lau, AS=rp00474 | en_HK |
dc.description.nature | link_to_OA_fulltext | - |
dc.identifier.doi | 10.1093/toxsci/kfn128 | en_HK |
dc.identifier.pmid | 18599499 | - |
dc.identifier.pmcid | PMC2721672 | - |
dc.identifier.scopus | eid_2-s2.0-52049095281 | en_HK |
dc.identifier.hkuros | 161110 | en_HK |
dc.relation.references | http://www.scopus.com/mlt/select.url?eid=2-s2.0-52049095281&selection=ref&src=s&origin=recordpage | en_HK |
dc.identifier.volume | 105 | en_HK |
dc.identifier.issue | 2 | en_HK |
dc.identifier.spage | 322 | en_HK |
dc.identifier.epage | 330 | en_HK |
dc.identifier.isi | WOS:000259207400009 | - |
dc.publisher.place | United Kingdom | en_HK |
dc.identifier.scopusauthorid | Gray, JS=13805652800 | en_HK |
dc.identifier.scopusauthorid | Bae, HK=24536787500 | en_HK |
dc.identifier.scopusauthorid | Li, JCB=23103447500 | en_HK |
dc.identifier.scopusauthorid | Lau, AS=7202626202 | en_HK |
dc.identifier.scopusauthorid | Pestka, JJ=7101824985 | en_HK |
dc.identifier.issnl | 1096-0929 | - |