Human peritoneal mesothelial cells synthesize interleukin-6: induction by IL-1 beta and TNF alpha.
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)
Topley
N
N
Institute of Nephrology, University of Wales College of Medicine, Cardiff Royal Infirmary, Wales, United Kingdom.
Jörres
A
A
Luttmann
W
W
Petersen
M M
MM
Lang
M J
MJ
Thierauch
K H
KH
Müller
C
C
Coles
G A
GA
Davies
M
M
Williams
J D
JD
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
D007375:Interleukin-1; D015850:Interleukin-6; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha