title: Loss of prostaglandin E2 release from immortalized urothelial cells obtained from interstitial cystitis patient bladders.
abstract: Interstitial cystitis (IC) is associated with increased activated mast cell numbers in the bladder and impairment of the barrier function of the urothelium. We stimulated immortalized urothelial cells derived from the inflamed region of IC bladders (SR22A or SM28 abn) or from healthy bladders (PD07i or PD08i) with tryptase and measured phospholipase A(2) (PLA(2)) activity and the resultant release of arachidonic acid and prostaglandin E(2) (PGE(2)). Tryptase stimulation of either PD07i or SR22A resulted in similar increases in PLA(2) activity and arachidonic acid release. However, tryptase stimulation of SR22A and SM28 abn did not result in a significant increase in PGE(2) release compared with the increase in PGE(2) release from tryptase-stimulated PD07i and PD08i cells. Expression of mRNA for cyclooxygenase-2 and PGE synthase was lower and mRNA for 15-hydroxyprostaglandin dehydrogenase was higher in SR22A compared with PD07i, suggesting that both decreased synthesis and increased metabolism are responsible for the lack of a PGE(2) response in tryptase-stimulated SR22A cells. Since PGE(2) is a cytoprotective eicosanoid, the failure to produce this metabolite in cells isolated from the IC bladder may represent an increased susceptibility to damage by proinfammatory stimuli.
authors.affiliation: Department of Pathology, Saint Louis University School of Medicine, Doisy Research Bldg., 3rd Floor, 1110 S. Grand Blvd., St. Louis, MO 63104, USA.
authors.forename: Prerna
authors.initials: P
authors.lastname: Rastogi
authors.forename: Alice
authors.initials: A
authors.lastname: Rickard
authors.forename: Nikolay
authors.initials: N
authors.lastname: Dorokhov
authors.forename: David J
authors.initials: DJ
authors.lastname: Klumpp
authors.forename: Jane
authors.initials: J
authors.lastname: McHowat
mesh_terms: D016718:Arachidonic Acid / Q000378:metabolism; D015820:Cadherins / Q000096:biosynthesis; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000096:biosynthesis; D018856:Cystitis, Interstitial / Q000378:metabolism* / Q000473:pathology; D019610:Cytoprotection / Q000502:physiology; D015232:Dinoprostone / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D054522:Group VI Phospholipases A2 / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D006911:Hydroxyprostaglandin Dehydrogenases / Q000096:biosynthesis; D019746:Intramolecular Oxidoreductases / Q000096:biosynthesis; D007633:Keratins / Q000096:biosynthesis; D054467:Phospholipases A2 / Q000378:metabolism; D000071876:Prostaglandin-E Synthases; D017510:Protein Folding; D053802:Tryptases / Q000378:metabolism; D001743:Urinary Bladder / Q000378:metabolism* / Q000473:pathology; D019459:Urothelium / Q000378:metabolism* / Q000473:pathology; D014945:Wound Healing / Q000502:physiology
chemical_list: D015820:Cadherins; D016718:Arachidonic Acid; D007633:Keratins; D006911:Hydroxyprostaglandin Dehydrogenases; D051546:Cyclooxygenase 2; D054522:Group VI Phospholipases A2; C516475:PLA2G6 protein, human; D054467:Phospholipases A2; D053802:Tryptases; D019746:Intramolecular Oxidoreductases; D000071876:Prostaglandin-E Synthases; D015232:Dinoprostone