Tumour necrosis factor alpha potentiates ion secretion induced by histamine in a human intestinal epithelial cell line and in mouse colon: involvement of the phospholipase D pathway.
OBJECTIVE
Patients suffering from inflammatory bowel disease show increased levels of the mast cell products histamine and tumour necrosis factor alpha (TNF-alpha). Treating these patients with antibodies against TNF-alpha diminishes the symptoms of diarrhoea. In this study, the effect of TNF-alpha on ion secretion induced by the mast cell mediator histamine in HT29cl.19A cells and mouse distal colon was investigated and the possible second messengers involved were studied.


METHODS
Electrophysiology of filter grown HT29cl.19A cells and isolated mouse distal colon was used to monitor the secretory response to histamine with and without prior exposure to TNF-alpha for 3-24 hours. Phospholipase D (PLD) activity and phosphatidic acid levels were analysed by 32P(i) labelling of HT29cl.19A cells.


RESULTS
In both experimental systems TNF-alpha was found to potentiate ion secretion induced by histamine. Phospholipid analysis of HT29cl.19A cells revealed that histamine activates the PLD pathway. Furthermore, TNF-alpha pretreated cells were found to have decreased phosphatidic acid levels, the intermediate product of the PLD pathway, which indicates upregulation of the enzyme phosphatidic acid phosphatase.


CONCLUSIONS
The mast cell products TNF-alpha and histamine synergistically stimulate ion secretion in intestinal epithelium via upregulation of the PLD pathway.
Oprins
J C J
JC
Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, the Netherlands. oprins@science.uva.nl
van der Burg
C
C
Meijer
H P
HP
Munnik
T
T
Groot
J A
JA
D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D018118:Chloride Channels / Q000187:drug effects* / Q000378:metabolism; D003106:Colon / Q000187:drug effects* / Q000502:physiology; D004357:Drug Synergism; D004594:Electrophysiology; D005260:Female; D006632:Histamine / Q000494:pharmacology*; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D010712:Phosphatidic Acids / Q000032:analysis; D010739:Phospholipase D / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D018118:Chloride Channels; D010712:Phosphatidic Acids; D014409:Tumor Necrosis Factor-alpha; D006632:Histamine; D010739:Phospholipase D