Endotoxin stimulates interleukin-6 production in intestinal epithelial cells. A synergistic effect with prostaglandin E2.
OBJECTIVE
To test the hypothesis that endotoxin stimulates the release of interleukin-6 (IL-6) from intestinal epithelial cells and that this effect of endotoxin is regulated by prostaglandin E2 (PGE2).


METHODS
A rat intestinal crypt cell line, IEC-6, was cultured in the presence of lipopolysaccharide (LPS), 0.1 to 1.0 microgram/mL, and/or PGE2, 1 mumol/L. In other experiments, indomethacin, 20 mumol/L, was added to LPS-treated cells to block the effects of prostaglandins. Control wells contained medium alone. Levels of IL-6 were determined by the B9 murine hybridoma bioassay. Polymerase chain reaction was performed on RNA from control and LPS-treated cells to examine IL-6 message.


RESULTS
Lipopolysaccharide and PGE2 induced IL-6 release from IEC-6 cells in a dose- and time-dependent fashion, and the substances interacted synergistically. Addition of indomethacin blunted the effect of endotoxin on IL-6 production, consistent with a stimulatory role of PGE2. Polymerase chain reaction demonstrated increased IL-6 messenger RNA in endotoxin-treated cells.


CONCLUSIONS
Endotoxin and PGE2 stimulate IL-6 production in IEC-6 cells and interact synergistically. The endotoxin-stimulated IL-6 release may be regulated at the transcriptional level.
Meyer
T A
TA
Department of Surgery, University of Cincinnati Medical Center, Ohio.
Noguchi
Y
Y
Ogle
C K
CK
Tiao
G
G
Wang
J J
JJ
Fischer
J E
JE
Hasselgren
P O
PO
D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D015232:Dinoprostone / Q000276:immunology* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004357:Drug Synergism; D004848:Epithelium; D004926:Escherichia coli; D007213:Indomethacin / Q000276:immunology / Q000494:pharmacology; D015850:Interleukin-6 / Q000032:analysis / Q000276:immunology / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000276:immunology*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats
D015850:Interleukin-6; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D015232:Dinoprostone; D007213:Indomethacin