PT  - JOURNAL ARTICLE
AU  - J C J Oprins
AU  - C van der Burg
AU  - H P Meijer
AU  - T Munnik
AU  - J A Groot
TI  - Tumour necrosis factor α potentiates ion secretion induced by histamine in a human intestinal epithelial cell line and in mouse colon: involvement of the phospholipase D pathway
AID  - 10.1136/gut.50.3.314
DP  - 2002 Mar 01
TA  - Gut
PG  - 314--321
VI  - 50
IP  - 3
4099  - http://gut.bmj.com/content/50/3/314.short
4100  - http://gut.bmj.com/content/50/3/314.full
SO  - Gut2002 Mar 01; 50
AB  - Background and aims: Patients suffering from inflammatory bowel disease show increased levels of the mast cell products histamine and tumour necrosis factor α (TNF-α). Treating these patients with antibodies against TNF-α diminishes the symptoms of diarrhoea. In this study, the effect of TNF-α 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-α for 3–24 hours. Phospholipase D (PLD) activity and phosphatidic acid levels were analysed by 32Pi labelling of HT29cl.19A cells.Results: In both experimental systems TNF-α was found to potentiate ion secretion induced by histamine. Phospholipid analysis of HT29cl.19A cells revealed that histamine activates the PLD pathway. Furthermore, TNF-α 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-α and histamine synergistically stimulate ion secretion in intestinal epithelium via upregulation of the PLD pathway.