title: Human peritoneal mesothelial cells synthesize interleukin-6: induction by IL-1 beta and TNF alpha.
abstract: Recent studies have demonstrated increased levels of IL-6 in the peritoneal cavity during CAPD peritonitis. The current investigation was initiated (i) to examine the human peritoneal mesothelial cell (HPMC) as a possible source of this secreted IL-6 and (ii) to characterize the released product and examine its regulation by other cytokines. Unstimulated HPMC under growth arrested conditions released IL-6 in a time dependent manner. After 24-hour HPMC IL-6 release (mean +/- SEM, N = 13) (expressed as pg/micrograms cell protein) was 1.67 +/- 0.33. Stimulation of HPMC with IL-1 beta or TNF alpha resulted in a time (increasing up to 48 hr) and dose dependent IL-6 generation. After 24 hours the levels induced by IL-1 beta and TNF alpha (both at 1000 pg/ml) were (mean +/- SEM, N = 13) 19.08 +/- 2.98 and 6.62 +/- 1.72, respectively. Stimulation with combinations of IL-1 beta and TNF alpha resulted in additive increases in IL-6 release. This release could be inhibited by co-incubation with anti-IL-1 beta and/or anti-TNF alpha antibodies. The level of released HPMC IL-6 measured by immunometric assay (ELISA) correlated directly with that detected in the 7TD1 IL-6 bioassay (r = 0.63; P < 0.001). Western blot analysis of concentrated HPMC supernatants using specific anti-IL-6 antibody demonstrated immunoreactive bands at 23 and 28 Kd following IL-1 beta or TNF alpha treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Institute of Nephrology, University of Wales College of Medicine, Cardiff Royal Infirmary, Wales, United Kingdom.
authors.forename: N
authors.initials: N
authors.lastname: Topley
authors.forename: A
authors.initials: A
authors.lastname: Jörres
authors.forename: W
authors.initials: W
authors.lastname: Luttmann
authors.forename: M M
authors.initials: MM
authors.lastname: Petersen
authors.forename: M J
authors.initials: MJ
authors.lastname: Lang
authors.forename: K H
authors.initials: KH
authors.lastname: Thierauch
authors.forename: C
authors.initials: C
authors.lastname: Müller
authors.forename: G A
authors.initials: GA
authors.lastname: Coles
authors.forename: M
authors.initials: M
authors.lastname: Davies
authors.forename: J D
authors.initials: JD
authors.lastname: Williams
mesh_terms: D001483:Base Sequence; D002478:Cells, Cultured; D004847:Epithelial Cells; D004848:Epithelium / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000235:genetics; D008969:Molecular Sequence Data; D010537:Peritoneum / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D007375:Interleukin-1; D015850:Interleukin-6; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha