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Conference Paper: Modulation of bacteria-induced sickness and inflammation by double-stranded RNA-dependent protein kinase (PKR)

TitleModulation of bacteria-induced sickness and inflammation by double-stranded RNA-dependent protein kinase (PKR)
Authors
Issue Date2013
PublisherInternational Stress and Behavior Society. The Conference website is located at http://www.stressandbehavior.com/
Citation
The 19th Annual International 'Stress and Behavior' Neuroscience and Biopsychiatry Conference (ISBS Conference), St. Petersburg, Russia, 16-19 May 2013. In Conference proceedings and program, 2013, p. 18 How to Cite?
AbstractINTRODUCTION: Sickness refers to a series of adaptive, physiological (e.g., fever) and behavioral (e.g., malaise, anorexia, social withdrawal, and fatigue) responses that collectively serve to facilitate recovery from systemic inflammation, i.e. infection and injury. However, there is also ample evidence indicating these sickness responses, if exacerbated, may precipitate depression and delirium. Hence, it will be advantageous to develop suitable approaches to modulate sickness so as to maximize its protective benefits and minimize its side effects. Since double-stranded RNA-dependent protein kinase (PKR) is an important kinase to regulate inflammation, the objective of this study is to investigate whether PKR also plays a regulatory role in sickness. METHODS: PKR+/+ and PKR-/- mice were infected subcutaneously with live Escherichia coli or vehicle. Fever, food consumption, and burrowing activity were assessed for 5 days as indices of sickness. The brain and the liver were harvested for quantitative polymerase chain reaction (qPCR) for expression of the inflammatory markers interleukin-1β (IL-1β) and cyclooxygenase (COX-2). RESULTS AND DISCUSSION: PKR-/- mice developed prolonged fever (3-4 days) when compared to PKR+/+ mice (2-3 days) following E. coli challenge. However, reductions in food consumption and burrowing did not display any significant difference between the two types of mice. E. coli led to elevations of IL-1β and COX-2 mRNA expression in the hypothalamus, hippocampus (IL-1β only), and the liver. While both types of mice exhibited similar increases in IL-1β (hypothalamus and hippocampus) and COX-2 (hypothalamus) in the brain, PKR-/- mice showed lesser increases of IL-1β and COX-2 in the liver than PKR +/+ mice. It has long been known that PKR participates in up-regulating inflammatory responses in immune cells, and that inflammatory factors such as IL-1β and COX-2 are key players in causing sickness during systemic inflammation. Yet, our data suggests that deficiency of PKR exaggerated fever, despite diminishing levels of inflammatory markers at the periphery. These surprising results shed light onto the suitability of whether manipulation of the immune-regulatory kinase PKR could serve as a therapeutic target to modulate sickness during infection.
DescriptionSymposium 4: Zofia Zukowska Sumposium on Experimental Models in Brain Research
Persistent Identifierhttp://hdl.handle.net/10722/184893

 

DC FieldValueLanguage
dc.contributor.authorPoon, CHen_US
dc.contributor.authorHo, YSen_US
dc.contributor.authorLok, CKMen_US
dc.contributor.authorLeung, MCen_US
dc.contributor.authorChiu, Ken_US
dc.contributor.authorChang, RCCen_US
dc.date.accessioned2013-07-15T10:16:41Z-
dc.date.available2013-07-15T10:16:41Z-
dc.date.issued2013en_US
dc.identifier.citationThe 19th Annual International 'Stress and Behavior' Neuroscience and Biopsychiatry Conference (ISBS Conference), St. Petersburg, Russia, 16-19 May 2013. In Conference proceedings and program, 2013, p. 18en_US
dc.identifier.urihttp://hdl.handle.net/10722/184893-
dc.descriptionSymposium 4: Zofia Zukowska Sumposium on Experimental Models in Brain Research-
dc.description.abstractINTRODUCTION: Sickness refers to a series of adaptive, physiological (e.g., fever) and behavioral (e.g., malaise, anorexia, social withdrawal, and fatigue) responses that collectively serve to facilitate recovery from systemic inflammation, i.e. infection and injury. However, there is also ample evidence indicating these sickness responses, if exacerbated, may precipitate depression and delirium. Hence, it will be advantageous to develop suitable approaches to modulate sickness so as to maximize its protective benefits and minimize its side effects. Since double-stranded RNA-dependent protein kinase (PKR) is an important kinase to regulate inflammation, the objective of this study is to investigate whether PKR also plays a regulatory role in sickness. METHODS: PKR+/+ and PKR-/- mice were infected subcutaneously with live Escherichia coli or vehicle. Fever, food consumption, and burrowing activity were assessed for 5 days as indices of sickness. The brain and the liver were harvested for quantitative polymerase chain reaction (qPCR) for expression of the inflammatory markers interleukin-1β (IL-1β) and cyclooxygenase (COX-2). RESULTS AND DISCUSSION: PKR-/- mice developed prolonged fever (3-4 days) when compared to PKR+/+ mice (2-3 days) following E. coli challenge. However, reductions in food consumption and burrowing did not display any significant difference between the two types of mice. E. coli led to elevations of IL-1β and COX-2 mRNA expression in the hypothalamus, hippocampus (IL-1β only), and the liver. While both types of mice exhibited similar increases in IL-1β (hypothalamus and hippocampus) and COX-2 (hypothalamus) in the brain, PKR-/- mice showed lesser increases of IL-1β and COX-2 in the liver than PKR +/+ mice. It has long been known that PKR participates in up-regulating inflammatory responses in immune cells, and that inflammatory factors such as IL-1β and COX-2 are key players in causing sickness during systemic inflammation. Yet, our data suggests that deficiency of PKR exaggerated fever, despite diminishing levels of inflammatory markers at the periphery. These surprising results shed light onto the suitability of whether manipulation of the immune-regulatory kinase PKR could serve as a therapeutic target to modulate sickness during infection.-
dc.languageengen_US
dc.publisherInternational Stress and Behavior Society. The Conference website is located at http://www.stressandbehavior.com/-
dc.relation.ispartofAnnual International 'Stress and Behavior' Neuroscience and Biopsychiatry Conference, ISBS Conferenceen_US
dc.titleModulation of bacteria-induced sickness and inflammation by double-stranded RNA-dependent protein kinase (PKR)en_US
dc.typeConference_Paperen_US
dc.identifier.emailHo, YS: janiceys@hku.hken_US
dc.identifier.emailLok, CKM: kmlok@hku.hken_US
dc.identifier.emailLeung, MC: saracml@hku.hken_US
dc.identifier.emailChiu, K: datwai@hkucc.hku.hken_US
dc.identifier.emailChang, RCC: rccchang@hku.hken_US
dc.identifier.authorityChiu, K=rp01973en_US
dc.identifier.hkuros215039en_US
dc.identifier.spage18en_US
dc.identifier.epage18en_US
dc.publisher.placeRussia-

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