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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<jats:sub>2<\/jats:sub> (PLA<jats:sub>2<\/jats:sub>) activity and the resultant release of arachidonic acid and prostaglandin E<jats:sub>2<\/jats:sub> (PGE<jats:sub>2<\/jats:sub>). Tryptase stimulation of either PD07i or SR22A resulted in similar increases in PLA<jats:sub>2<\/jats:sub> activity and arachidonic acid release. However, tryptase stimulation of SR22A and SM28 abn did not result in a significant increase in PGE<jats:sub>2<\/jats:sub> release compared with the increase in PGE<jats:sub>2<\/jats:sub> 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<jats:sub>2<\/jats:sub> response in tryptase-stimulated SR22A cells. 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