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The involvement of prostaglandin E2 in interleukin-1β evoked anorexia is strain dependent
Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Intensive Care in Linköping.
Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
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2016 (English)In: Brain, behavior, and immunity, ISSN 0889-1591, E-ISSN 1090-2139Article in journal (Refereed) In press
Abstract [en]

From experiments in mice in which the prostaglandin E2 (PGE2) synthesizing enzyme mPGES-1 was genetically deleted, as well as from experiments in which PGE2 was injected directly into the brain, PGE2 has been implicated as a mediator of inflammatory induced anorexia. Here we aimed at examining which PGE2 receptor (EP1–4) that was critical for the anorexic response to peripherally injected interleukin-1β (IL-1β). However, deletion of neither EP receptor in mice, either globally (for EP1, EP2, and EP3) or selectively in the nervous system (EP4), had any effect on the IL-1β induced anorexia. Because these mice were all on a C57BL/6 background, whereas previous observations demonstrating a role for induced PGE2 in IL-1β evoked anorexia had been carried out on mice on a DBA/1 background, we examined the anorexic response to IL-1β in mice with deletion of mPGES-1 on a C57BL/6 background and a DBA/1 background, respectively. We confirmed previous findings that mPGES-1 knock-out mice on a DBA/1 background displayed attenuated anorexia to IL-1β; however, mice on a C57BL/6 background showed the same profound anorexia as wild type mice when carrying deletion of mPGES-1, while displaying almost normal food intake after pretreatment with a cyclooxygenase-2 inhibitor. We conclude that the involvement of induced PGE2 in IL-1β evoked anorexia is strain dependent and we suggest that different routes that probably involve distinct prostanoids exist by which inflammatory stimuli may evoke an anorexic response and that these routes may be of different importance in different strains of mice.

Place, publisher, year, edition, pages
2016.
Keyword [en]
Anorexia, Prostaglandin E2, EP receptors, Interleukin-1, Cyclooxygenase-2, Mice
National Category
Immunology Cell Biology Pharmacology and Toxicology
Identifiers
URN: urn:nbn:se:liu:diva-132639DOI: 10.1016/j.bbi.2016.06.014PubMedID: 27375005OAI: oai:DiVA.org:liu-132639DiVA: diva2:1047665
Available from: 2016-11-18 Created: 2016-11-18 Last updated: 2016-11-23Bibliographically approved
In thesis
1. Mechanisms Behind Illness-Induced Anorexia
Open this publication in new window or tab >>Mechanisms Behind Illness-Induced Anorexia
2016 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Loss of appetite is together with fever and malaise hallmarks of infection. Loosing appetite during an acute infection such as influenza does not result in any longlasting effects, but loosing appetite during chronic diseases such as cancer or AIDS constitutes a risk factor for mortality. Food intake regulation during inflammation is orchestrated by the brain in response to peripheral inflammatory signals. It is known that expression of the prostaglandin synthesizing enzyme cyclooxygenase 2 (COX-2) is crucial for the mechanisms underlying inflammation-induced anorexia, and that prostaglandin E2 (PGE2) is involved in anorexia induced by interleukin-1 beta (IL-1β). In this thesis I examined the prostaglandin-pathways proposed to be involved in anorexia. We show that acute anorexia is dependent on COX-2 expression, while cancer-induced anorexia is mediated by cyclooxygenase 1 (COX-1), at least in the initial stages, suggesting that the signaling pathways for chronic- and acute anorexia are distinct. We were able to demonstrate that the pathway underlying acute anorexia is distinct from that of fever, and that taste aversion is prostaglandin independent. We could also show that both acute and chronic anorexia-cachexia is dependent on expression of myeloid differentiation primary response gene (MyD88) in hematopoietic/myeloid cells.

In summary, the findings presented in this thesis suggest that anorexia is a result of many different signaling pathways, as opposed to what is the case for several other inflammatory symptoms such as fever and malaise, where the pathways have been shown to be very exclusive. This provides new insight into the diversity of the pathways underlying inflammatory symptoms, which is fundamental for the ability to present potential, symptom-specific drug targets.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2016. 79 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1549
National Category
Cell and Molecular Biology Neurosciences
Identifiers
urn:nbn:se:liu:diva-132640 (URN)10.3384/diss.diva-132640 (DOI)9789176856482 (Print) (ISBN)
Public defence
2016-12-09, Berzeliussalen, Campus US, Linköping, 13:00 (Swedish)
Opponent
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Available from: 2016-11-18 Created: 2016-11-18 Last updated: 2016-11-21Bibliographically approved

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Nilsson, AnnaElander, LouiseHallbeck, MartinÖrtegren Kugelberg, UnnEngblom, DavidBlomqvist, Anders
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Division of Cell BiologyFaculty of Medicine and Health SciencesDepartment of Anaesthesiology and Intensive Care in LinköpingDivision of Neuro and Inflammation ScienceDepartment of Clinical Pathology and Clinical Genetics
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