Defective arachidonate release and PGE2 production in Gi alpha2-deficient intestinal and colonic subepithelial myofibroblasts

Inflammatory Bowel Diseases
Robert A Edwards, Andrew Zoller Smock

Abstract

Mice lacking the pertussis toxin-sensitive G-protein subunit Gi alpha2 spontaneously develop colitis and colon cancer. In the gut, arachidonate-derived prostaglandin E2 (PGE2) modulates intestinal immune responses and epithelial restitution and is derived largely from subepithelial myofibroblasts. We tested whether known decreases in arachidonate release in cells lacking Gi alpha2 would result in decreased PGE2 production and tissue PGE2 levels. PGE2 levels were significantly decreased in the colon of Gi alpha2-/- mice. Gi alpha2-/- myofibroblasts from the small intestine and colon both released asymptotically equal to 50% less arachidonate and 3- to 7-fold less PGE2 and 6-keto PGF1alpha in response to adenosine triphosphate, thrombin, tumor necrosis factor-alpha, or lipopolysaccharide, in a partially cyclooxygenase (COX)-2-dependent manner. Decreased arachidonate release did not appear to be caused by a defect in cPLA2 translocation in the absence of Gi alpha2. Basal myofibroblast COX-1 and COX-2 expression was downregulated in Gi alpha2-/- cells. No differences in proliferation rates were found between serum-starved or serum-activated wild-type (WT) and Gi alpha2-/- myofibroblasts. Finally, treatment of Gi alpha2-/- mice with...Continue Reading

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Citations

Mar 15, 2008·Inflammatory Bowel Diseases·Robert A EdwardsLutz Birnbaumer
Apr 9, 2013·Archivum Immunologiae Et Therapiae Experimentalis·Yantang WangGuixiu Shi
Jun 8, 2014·Inflammopharmacology·Nidhi GoyalPuneet Kumar
Jul 31, 2013·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Salud Pérez-GutiérrezErnesto Sánchez-Mendoza
Mar 3, 2007·American Journal of Physiology. Gastrointestinal and Liver Physiology·Brian HoangRobert A Edwards
Aug 16, 2008·American Journal of Physiology. Gastrointestinal and Liver Physiology·Takashi OhamaHiroshi Ozaki
Oct 24, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jamal I SaadaDon W Powell
Jul 21, 2007·American Journal of Physiology. Gastrointestinal and Liver Physiology·J F Di MariD W Powell

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