title: Selective CB2 up-regulation in women affected by endometrial inflammation.
abstract: Endometritis is defined as an inflammation of the endometrial mucosa of the uterus. In endometritis large amounts of toxic mediators, including nitric oxide (NO) are released by inflammatory cells. As a consequence of nitric oxide-dependent injury, the cells respond by triggering protective mechanisms, by changing the endocannabinoid system (ECS) which comprises both CB(1) and CB(2) cannabinoid receptors and their endogenous ligands. The aim of our study was to seek out evidence for the presence of cannabinoid receptors in inflammatory endometrial tissue as well as for their potential role in endometrial inflammation. Our results showed a selective up-regulation of both transcription and expression of CB(2) receptors in biopsies from women affected by endometrial inflammation compared to healthy women. The experiments with the nitric oxide-donor S-Nitroso-L-Glutathione (GSNO) suggest that such a selective up-regulation may be related to the nitric oxide release occurring during endometrial inflammation. In addition, we demonstrated an increase in chymase expression, a marker of mast cells, in biopsies of women affected by endometritis. Therefore our results support the hypothesis that the up-regulation of CB(2) occurs mainly on mast cells and that it might tend to sensitize these cells to the anti-inflammatory effect exerted by endogenous cannabinoids by binding their receptor and thus preventing the mast cell degranulation and the release of pro-inflammatory mediators. In conclusion, we believe that the selective CB(2) up-regulation might play a role as a novel prognostic factor in endometrial inflammation.
authors.affiliation: Endocannabinoid Research Group, Department of Experimental Pharmacology, Faculty of Pharmacy, University of Naples, Federico II, Naples, Italy. iuvone@unina.it
authors.forename: Teresa
authors.initials: T
authors.lastname: Iuvone
authors.forename: Daniele
authors.initials: D
authors.lastname: De Filippis
authors.forename: Attilio
authors.initials: A
authors.lastname: Di Spiezio Sardo
authors.forename: Alessandra
authors.initials: A
authors.lastname: D'Amico
authors.forename: Sara
authors.initials: S
authors.lastname: Simonetti
authors.forename: Stefania
authors.initials: S
authors.lastname: Sparice
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Esposito
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Bifulco
authors.forename: Luigi
authors.initials: L
authors.lastname: Insabato
authors.forename: Carmine
authors.initials: C
authors.lastname: Nappi
authors.forename: Maurizio
authors.initials: M
authors.lastname: Guida
mesh_terms: D001706:Biopsy; D000001:Calcimycin / Q000494:pharmacology; D016022:Case-Control Studies; D015550:Cell Degranulation / Q000187:drug effects; D053818:Chymases / Q000378:metabolism; D004716:Endometritis / Q000473:pathology* / Q000503:physiopathology* / Q000601:surgery; D005260:Female; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology; D008407:Mast Cells / Q000502:physiology; D020030:Nitric Oxide Donors / Q000494:pharmacology; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D009573:Nitrites / Q000032:analysis; D009924:Organ Culture Techniques; D009195:Peroxidase / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D043885:Receptor, Cannabinoid, CB2; D026422:S-Nitrosoglutathione / Q000494:pharmacology; D014158:Transcription, Genetic; D015854:Up-Regulation; D001619:beta-N-Acetylhexosaminidases / Q000032:analysis
chemical_list: D007211:Indoles; D007476:Ionophores; D020030:Nitric Oxide Donors; D009573:Nitrites; D012333:RNA, Messenger; D043885:Receptor, Cannabinoid, CB2; D000001:Calcimycin; D026422:S-Nitrosoglutathione; D009195:Peroxidase; D052247:Nitric Oxide Synthase Type II; D001619:beta-N-Acetylhexosaminidases; D053818:Chymases; C402944:JHW 015