title: Human peritoneal mesothelial cell prostaglandin synthesis: induction of cyclooxygenase mRNA by peritoneal macrophage-derived cytokines.
abstract: Increasing evidence suggests that the mesothelial cell contributes to the control of inflammation in both the normal and inflamed peritoneal cavity. The present study examines the regulation of prostaglandin production by human peritoneal mesothelial cells (HPMC) following stimulation with peritoneal macrophage-conditioned medium and the cytokines interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha). IL-1 beta and TNF-alpha stimulated significant release of prostaglandin above background levels in a time and dose dependent manner. Stimulation of HPMC with IL-1 beta (500 pg/ml) or TNF-alpha (100 pg/ml) for 24 hours resulted in the release of 24.5 +/- 4.3 (N = 11) (z = 3.40, P < 0.001 vs. control) and 19.4 +/- 4.5 (N = 10; z = 3.29, P < 0.001 vs. control) pg 6-keto-PGF1 a/micrograms cellular protein, respectively. Pretreatment of HPMC with dexamethasone (10(-6) to 10(-9) M) inhibited both constitutive and cytokine stimulated prostaglandin synthesis in a dose dependent manner. Both PMø-CM and PMø-S.epiCM stimulated 6-keto-PGF1 alpha and PGE2 synthesis by HPMC in a time and dose dependent manner (PMø-S.epiCM >> PMø-CM). Co-incubation of HPMC with PMø-S.epiCM in the presence of anti-IL-1 beta and/or anti-TNF-alpha antibody, interleukin-1 receptor antagonist or soluble TNF receptor (TNF p75) significantly reduced the capacity of these supernatants to stimulate prostaglandin synthesis. Exposure of HPMC to cytokines or PMø-S.epiCM resulted in the time dependent increase in the levels of both Cox-1 and Cox-2 mRNA as assessed by RT/PCR analysis with the greatest increase being seen for Cox-2. These data demonstrate specific stimulation of eicosanoid metabolism in HPMC by peritoneal macrophage derived cytokines, indicating the possible importance of these mediators in the activation of intraperitoneal prostaglandin synthesis. HPMC prostaglandins might act as important pro/anti-inflammatory mediators contributing to a cytokine network in the peritoneal cavity during CAPD peritonitis.
authors.affiliation: Institute of Nephrology, University of Wales College of Medicine, Cardiff Royal Infirmary, United Kingdom.
authors.forename: N
authors.initials: N
authors.lastname: Topley
authors.forename: M M
authors.initials: MM
authors.lastname: Petersen
authors.forename: R
authors.initials: R
authors.lastname: Mackenzie
authors.forename: A
authors.initials: A
authors.lastname: Neubauer
authors.forename: E
authors.initials: E
authors.lastname: Stylianou
authors.forename: V
authors.initials: V
authors.lastname: Kaever
authors.forename: M
authors.initials: M
authors.lastname: Davies
authors.forename: G A
authors.initials: GA
authors.lastname: Coles
authors.forename: A
authors.initials: A
authors.lastname: Jörres
authors.forename: J D
authors.initials: JD
authors.lastname: Williams
mesh_terms: D001483:Base Sequence; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D017077:Culture Media, Conditioned; D016207:Cytokines / Q000276:immunology*; D017931:DNA Primers; D004790:Enzyme Induction / Q000187:drug effects; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D008264:Macrophages / Q000276:immunology / Q000378:metabolism*; D008969:Molecular Sequence Data; D010529:Peritoneal Cavity / Q000166:cytology; D010537:Peritoneum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis* / Q000235:genetics; D011453:Prostaglandins / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000096:biosynthesis*; D011863:Radioimmunoassay
chemical_list: D017077:Culture Media, Conditioned; D016207:Cytokines; D017931:DNA Primers; D011453:Prostaglandins; D012333:RNA, Messenger; D011451:Prostaglandin-Endoperoxide Synthases