title: The endogenous cannabinoid system in the gut of patients with inflammatory bowel disease.
abstract: Activation of cannabinoid receptors (CBs) by endocannabinoids impacts on a number of gastrointestinal functions. Recent data indicate that CB1 agonists improve 2,4-dinitrobenzene sulfonic acid-induced colitis in mice, thus suggesting a role for the endocannabinoid agonist anandamide (AEA) in protecting the gut against inflammation. We here examined the gut endocannabinoid system in inflammatory bowel disease (IBD) patients, and investigated the ex vivo and in vitro effects of the non-hydrolysable AEA analog methanandamide (MAEA) on the mucosal proinflammatory response. The content of AEA, but not of 2-arachidonoyl-glycerol and N-palmitoylethanolamine, was significantly lower in inflamed than uninflamed IBD mucosa, and this was paralleled by lower activity of the AEA-synthesizing enzyme N-acyl-phosphatidylethanolamine-specific phospholipase D and higher activity of the AEA-degrading enzyme fatty acid amide hydrolase. MAEA significantly downregulated interferon-γ and tumor necrosis factor-α secretion by both organ culture biopsies and lamina propria mononuclear cells. Although these results are promising, further studies are needed to determine the role of cannabinoid pathways in gut inflammation.
authors.affiliation: First Department of Medicine, Fondazione IRCCS Policlinico S. Matteo, Centro per lo Studio e la Cura delle Malattie Infiammatorie Croniche Intestinali, University of Pavia, Pavia, Italy. a.disabatino@smatteo.pv.it
authors.forename: A
authors.initials: A
authors.lastname: Di Sabatino
authors.forename: N
authors.initials: N
authors.lastname: Battista
authors.forename: P
authors.initials: P
authors.lastname: Biancheri
authors.forename: C
authors.initials: C
authors.lastname: Rapino
authors.forename: L
authors.initials: L
authors.lastname: Rovedatti
authors.forename: G
authors.initials: G
authors.lastname: Astarita
authors.forename: A
authors.initials: A
authors.lastname: Vanoli
authors.forename: E
authors.initials: E
authors.lastname: Dainese
authors.forename: M
authors.initials: M
authors.lastname: Guerci
authors.forename: D
authors.initials: D
authors.lastname: Piomelli
authors.forename: S L F
authors.initials: SL
authors.lastname: Pender
authors.forename: T T
authors.initials: TT
authors.lastname: MacDonald
authors.forename: M
authors.initials: M
authors.lastname: Maccarrone
authors.forename: G R
authors.initials: GR
authors.lastname: Corazza
mesh_terms: D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology; D063385:Cannabinoid Receptor Modulators / Q000378:metabolism*; D016207:Cytokines / Q000096:biosynthesis; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000378:metabolism* / Q000473:pathology; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000473:pathology; D007422:Intestines / Q000473:pathology; D051379:Mice; D058628:Myofibroblasts / Q000187:drug effects / Q000378:metabolism; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism; D043885:Receptor, Cannabinoid, CB2 / Q000378:metabolism; D050797:STAT4 Transcription Factor / Q000378:metabolism; D020825:T-Box Domain Proteins / Q000378:metabolism; D000098815:T-bet Transcription Factor
chemical_list: D001095:Arachidonic Acids; D063385:Cannabinoid Receptor Modulators; D016207:Cytokines; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; D050797:STAT4 Transcription Factor; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; C088155:methanandamide