CCK1-receptor stimulation protects against gut mediator-induced lung damage during endotoxemia

Friederike Eisner, Elizabeth M. Martin, Markus A. Küper, Helen E Raybould, Jörg Glatzle

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1878-1890
Number of pages13
JournalCellular Physiology and Biochemistry
Volume32
Issue number6
DOIs
StatePublished - 2013

Keywords

  • Cholecystokinin
  • Cholinergic anti-inflammatory pathway
  • Endotoxemia
  • Innate immunity
  • Mucosal immunity
  • Sepsis

ASJC Scopus subject areas

  • Physiology

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