Article Text
Abstract
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.
- tumour necrosis factor α
- intestinal epithelia
- histamine
- ion secretion
- phospholipase D
- TNF-α, tumour necrosis factor α
- PKC, protein kinase C
- DAG, 1,2-diacylglycerol
- PLD, phospholipase D
- PA, phosphatidic acid
- PAP, PA phosphatase
- PBut, phosphatidylbutanol
- IBD, inflammatory bowel disease
- Vt, transepithelial potential
- Va, intracellular potential
- Isc, short circuit current
- Rt, transepithelial resistance
- fRa, fractional resistance
- PIP2, phosphatidylinositol 4,5-bisphospate
- TTX, tetrodotoxin
- IFN-γ, interferon γ
- IP3, inositol 1,4,5-trisphosphate
Statistics from Altmetric.com
- TNF-α, tumour necrosis factor α
- PKC, protein kinase C
- DAG, 1,2-diacylglycerol
- PLD, phospholipase D
- PA, phosphatidic acid
- PAP, PA phosphatase
- PBut, phosphatidylbutanol
- IBD, inflammatory bowel disease
- Vt, transepithelial potential
- Va, intracellular potential
- Isc, short circuit current
- Rt, transepithelial resistance
- fRa, fractional resistance
- PIP2, phosphatidylinositol 4,5-bisphospate
- TTX, tetrodotoxin
- IFN-γ, interferon γ
- IP3, inositol 1,4,5-trisphosphate