Journal article

Publication year: 2019

Journal: European Journal of Pharmacology

Volume number: 864

ISSN: 0014-2999

eISSN: 1879-0712

DOI Link: https://doi.org/10.1016/j.ejphar.2019.172713

Publisher: Elsevier

Abstract: 

The role of mast cells during inflammatory bowel diseases (IBD) is discussed controversially. Whereas several studies report an increase in mast cell density during IBD, others found a decrease. Recently, we observed a reduced response to mast cell degranulation induced by antigen contact in a colitis model. As the effects of mast cell mediators on epithelial ion transport are mediated indirectly via stimulation of secretomotor neurons, we investigated in vitro whether proinflammatory cytokines change the response to mast cell degranulation.

Tumor necrosis factor alpha (TNF alpha) and a mix of proinflammatory cytokines caused an increase of short-circuit current (I-sc) and tissue conductance in rat colon. Anion secretion induced by histamine was downregulated in the presence of interleukin-1 beta (IL-1 beta) and the cytokine mix, whereas the response to the mast cell stimulator compound 48/80 was not changed significantly. In a coculture of rat submucosal ganglionic cells with a mast cell line (RBL-2H3), TNF alpha preincubation for 1 d increased the percentage of neurons responding to mast cell degranulation with an increase of the cytosolic Ca2+ concentration and enhanced the amplitude of this response. Consequently, the downregulation of epithelial secretion is compensated by an increased sensitivity of secretomotor neurons leading to a constant response of the epithelium to compound 48/80. Furthermore, enteric neurons can modify mast cell functions as nicotine inhibited the increase in cytosolic Ca2+ concentration of RBL-2H3 cells and the I-sc evoked by compound 48/80. Consequently, these in vitro models deliver new insights into cellular interactions in the gut wall under inflammatory conditions.

Harvard Citation style: Ballout, J. and Diener, M. (2019) Interactions between rat submucosal neurons and mast cells are modified by cytokines and neurotransmitters, European Journal of Pharmacology, 864, Article 172713. https://doi.org/10.1016/j.ejphar.2019.172713

APA Citation style: Ballout, J., & Diener, M. (2019). Interactions between rat submucosal neurons and mast cells are modified by cytokines and neurotransmitters. European Journal of Pharmacology. 864, Article 172713. https://doi.org/10.1016/j.ejphar.2019.172713