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Eur J Pharmacol. 2012 Jan 30;675(1-3):57-62. doi: 10.1016/j.ejphar.2011.11.035. Epub 2011 Dec 8.

C-Kit controls IL-1β-induced effector functions in HMC-cells.

Author information

1
Institut für Immunologie, Universitätsklinikum Jena-Friedrich-Schiller-Universität Jena, 07743 Jena, Germany. Sebastian.Drube@mti.uni-jena.de

Abstract

The receptor tyrosine kinase c-Kit is important for mast cell differentiation, proliferation, and cytokine release. Recently, we reported that c-Kit acts as an intermediate signalling molecule regulating IL-33-induced signalling and effector functions in mast cells. Here, we investigated the influence of c-Kit on the IL-1β-induced signalling and effector functions in HMC mast cell lines. HMC-cells were stimulated with IL-1β and the resulting signalling and cytokine responses were analysed. Furthermore, we used pharmacological inhibitors to investigate the relevance of several signalling molecules for the IL-1β-induced signalling and cytokine responses. Treatment of HMC-cells with the c-Kit inhibitor STI571 blocked the IL-1β-induced activation of Erk1/2 and JNK1/2 but not p38 and NFκB. Furthermore, inhibition of these signalling pathways blocked the IL-6 production in HMC-cells. These findings indicate that IL-1β-induced signalling in mast cells branches into c-Kit- dependent and -independent pathways, both relevant for IL-6 release. Therefore, c-Kit is an important regulator of IL-1 receptor 1-induced signalling and effector functions in HMC-cells.

PMID:
22173128
DOI:
10.1016/j.ejphar.2011.11.035
[Indexed for MEDLINE]

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