title: C-Kit controls IL-1β-induced effector functions in HMC-cells.
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.
authors.affiliation: Institut für Immunologie, Universitätsklinikum Jena-Friedrich-Schiller-Universität Jena, 07743 Jena, Germany. Sebastian.Drube@mti.uni-jena.de
authors.forename: Sebastian
authors.initials: S
authors.lastname: Drube
authors.forename: Frederike
authors.initials: F
authors.lastname: Schmitz
authors.forename: Christiane
authors.initials: C
authors.lastname: Göpfert
authors.forename: Franziska
authors.initials: F
authors.lastname: Weber
authors.forename: Thomas
authors.initials: T
authors.lastname: Kamradt
mesh_terms: D000818:Animals; D001549:Benzamides; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate; D053583:Interleukin-1beta / Q000819:agonists / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010879:Piperazines / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D019009:Proto-Oncogene Proteins c-kit / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011743:Pyrimidines / Q000494:pharmacology; D017472:Receptors, Interleukin-1 / Q000819:agonists / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013047:Specific Pathogen-Free Organisms; D000093242:Interleukin-6 Inhibitors
chemical_list: D001549:Benzamides; D016207:Cytokines; D000068877:Imatinib Mesylate; D053583:Interleukin-1beta; D015850:Interleukin-6; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D019009:Proto-Oncogene Proteins c-kit; D011743:Pyrimidines; D017472:Receptors, Interleukin-1; D000093242:Interleukin-6 Inhibitors