CCK1-Receptor Stimulation Protects Against Gut Mediator-Induced Lung Damage During Endotoxemia
Background/Aims: Cholecystokinin 1-receptor (CCK1-R) activation by long chain fatty acid (LCFA) absorption stimulates vago-vagal reflex pathways in the brain stem. The present study determines whether this reflex also activates the cholinergic anti-inflammatory pathway, a pathway known to modulate c...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Cell Physiol Biochem Press GmbH & Co KG
2013-12-01
|
| Series: | Cellular Physiology and Biochemistry |
| Subjects: | |
| Online Access: | http://www.karger.com/Article/FullText/356644 |
| _version_ | 1818927877704384512 |
|---|---|
| author | Friederike Eisner Elizabeth M. Martin Markus A. Küper Helen E. Raybould Jörg Glatzle |
| author_facet | Friederike Eisner Elizabeth M. Martin Markus A. Küper Helen E. Raybould Jörg Glatzle |
| author_sort | Friederike Eisner |
| collection | DOAJ |
| description | Background/Aims: Cholecystokinin 1-receptor (CCK1-R) activation by long chain fatty acid (LCFA) absorption stimulates vago-vagal reflex pathways in the brain stem. The present study determines whether this reflex also activates the cholinergic anti-inflammatory pathway, a pathway known to modulate cytokine release during endotoxemia. Methods:Mesenteric lymph was obtained from wild type (WT) and CCK1-R knockout (CCK1-R-/-) mice intraperitoneally challenged with Lipopolysaccharid (LPS) (endotoxemic lymph, EL) and intestinally infused with vehicle or LCFA-enriched solution. The lymph was analyzed for TNFα, IL-6 and IL-10 concentration and administered to healthy recipient mice via jugular infusion. Alveolar wall thickness, myeloperoxidase (MPO) and TUNEL positive cells were determined in lung tissue of recipient mice. Results: LCFA infusion in WT mice reduced TNFα concentration in EL by 49% compared to vehicle infusion, but had no effect in CCK1-R-/- mice. EL significantly increased the alveolar wall thickness, the number of MPO-positive and TUNEL-positive cells compared to control lymph administration. LCFA infusion in WT, but not in CCK1R-/- mice, significantly reduced these pathological effects of EL. Conclusion: During endotoxemia enteral LCFA absorption reduces TNFα release into mesenteric lymph and attenuates histomorphologic parameters of lung dysfunction. Failure to elicit this effect in CCK1R-/- mice demonstrates that anti-inflammatory properties of LCFAs are mediated through CCK1-Rs. |
| first_indexed | 2024-12-20T03:20:00Z |
| format | Article |
| id | doaj.art-7ecdc7556eb842839430f60fc87678de |
| institution | Directory Open Access Journal |
| issn | 1015-8987 1421-9778 |
| language | English |
| last_indexed | 2024-12-20T03:20:00Z |
| publishDate | 2013-12-01 |
| publisher | Cell Physiol Biochem Press GmbH & Co KG |
| record_format | Article |
| series | Cellular Physiology and Biochemistry |
| spelling | doaj.art-7ecdc7556eb842839430f60fc87678de2022-12-21T19:55:15ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782013-12-013261878189010.1159/000356644356644CCK1-Receptor Stimulation Protects Against Gut Mediator-Induced Lung Damage During EndotoxemiaFriederike EisnerElizabeth M. MartinMarkus A. KüperHelen E. RaybouldJörg GlatzleBackground/Aims: Cholecystokinin 1-receptor (CCK1-R) activation by long chain fatty acid (LCFA) absorption stimulates vago-vagal reflex pathways in the brain stem. The present study determines whether this reflex also activates the cholinergic anti-inflammatory pathway, a pathway known to modulate cytokine release during endotoxemia. Methods:Mesenteric lymph was obtained from wild type (WT) and CCK1-R knockout (CCK1-R-/-) mice intraperitoneally challenged with Lipopolysaccharid (LPS) (endotoxemic lymph, EL) and intestinally infused with vehicle or LCFA-enriched solution. The lymph was analyzed for TNFα, IL-6 and IL-10 concentration and administered to healthy recipient mice via jugular infusion. Alveolar wall thickness, myeloperoxidase (MPO) and TUNEL positive cells were determined in lung tissue of recipient mice. Results: LCFA infusion in WT mice reduced TNFα concentration in EL by 49% compared to vehicle infusion, but had no effect in CCK1-R-/- mice. EL significantly increased the alveolar wall thickness, the number of MPO-positive and TUNEL-positive cells compared to control lymph administration. LCFA infusion in WT, but not in CCK1R-/- mice, significantly reduced these pathological effects of EL. Conclusion: During endotoxemia enteral LCFA absorption reduces TNFα release into mesenteric lymph and attenuates histomorphologic parameters of lung dysfunction. Failure to elicit this effect in CCK1R-/- mice demonstrates that anti-inflammatory properties of LCFAs are mediated through CCK1-Rs.http://www.karger.com/Article/FullText/356644SepsisEndotoxemiaInnate immunityMucosal immunityCholinergic anti-inflammatory pathwayCholecystokinin |
| spellingShingle | Friederike Eisner Elizabeth M. Martin Markus A. Küper Helen E. Raybould Jörg Glatzle CCK1-Receptor Stimulation Protects Against Gut Mediator-Induced Lung Damage During Endotoxemia Cellular Physiology and Biochemistry Sepsis Endotoxemia Innate immunity Mucosal immunity Cholinergic anti-inflammatory pathway Cholecystokinin |
| title | CCK1-Receptor Stimulation Protects Against Gut Mediator-Induced Lung Damage During Endotoxemia |
| title_full | CCK1-Receptor Stimulation Protects Against Gut Mediator-Induced Lung Damage During Endotoxemia |
| title_fullStr | CCK1-Receptor Stimulation Protects Against Gut Mediator-Induced Lung Damage During Endotoxemia |
| title_full_unstemmed | CCK1-Receptor Stimulation Protects Against Gut Mediator-Induced Lung Damage During Endotoxemia |
| title_short | CCK1-Receptor Stimulation Protects Against Gut Mediator-Induced Lung Damage During Endotoxemia |
| title_sort | cck1 receptor stimulation protects against gut mediator induced lung damage during endotoxemia |
| topic | Sepsis Endotoxemia Innate immunity Mucosal immunity Cholinergic anti-inflammatory pathway Cholecystokinin |
| url | http://www.karger.com/Article/FullText/356644 |
| work_keys_str_mv | AT friederikeeisner cck1receptorstimulationprotectsagainstgutmediatorinducedlungdamageduringendotoxemia AT elizabethmmartin cck1receptorstimulationprotectsagainstgutmediatorinducedlungdamageduringendotoxemia AT markusakuper cck1receptorstimulationprotectsagainstgutmediatorinducedlungdamageduringendotoxemia AT heleneraybould cck1receptorstimulationprotectsagainstgutmediatorinducedlungdamageduringendotoxemia AT jorgglatzle cck1receptorstimulationprotectsagainstgutmediatorinducedlungdamageduringendotoxemia |