Human peritoneal mesothelial cells synthesize interleukin-6: Induction by IL-1beta and TNFalpha

Topley, Nicholas, Jörres, Achim, Luttmann, Werner, Petersen, Meryl M., Lang, M. Janine, Thierauch, Karl-Heinz, Müller, Christian, Coles, Gerald A., Davies, Malcolm and Williams, John D. 1993. Human peritoneal mesothelial cells synthesize interleukin-6: Induction by IL-1beta and TNFalpha. Kidney International 43 (1) , pp. 226-233. 10.1038/ki.1993.36

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Abstract

Human peritoneal mesothelial cells synthesize interleukin-6: Induction by IL-1beta and TNFalpha. 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 plusminus sem, N = 13) (expressed as pg/mug cell protein) was 1.67 plusminus 0.33. Stimulation of HPMC with IL-1beta or TNFalpha resulted in a time (increasing up to 48 hr) and dose dependent IL-6 generation. After 24 hours the levels induced by IL-1beta and TNFalpha (both at 1000 pg/ml) were (mean plusminus sem, N = 13) 19.08 plusminus 2.98 and 6.62 plusminus 1.72, respectively. Stimulation with combinations of IL-1beta and TNFalpha resulted in additive increases in IL-6 release. This release could be inhibited by coincubation with anti-IL-1beta and/or anti-TNFalpha 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-1beta or TNFalpha treatment. PCR amplification of reverse transcribed HPMC mRNA using specific IL-6 primers demonstrated a single 465 base pair transcript, the expression of which was enhanced in a time dependent manner following treatment of HPMC with either IL-1beta or TNFalpha. These data demonstrate for the first time that HPMC synthesize IL-6 and that its release can be regulated as a result of increased expression of specific mRNA and de novo protein synthesis by other cytokines. HPMC derived IL-6 might contribute directly to the cytokine network regulating intraperitoneal inflammatory responses associated with bacterial peritonitis.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine Systems Immunity Research Institute (SIURI)
Subjects:	R Medicine > RC Internal medicine R Medicine > RM Therapeutics. Pharmacology
Publisher:	Nature Publishing Group
ISSN:	0085-2538
Last Modified:	30 Jun 2017 03:03
URI:	https://orca.cardiff.ac.uk/id/eprint/46379

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