Murine bone marrow-derived mast cells as potent producers of IL-9: costimulatory function of IL-10 and kit ligand in the presence of IL-1.
Recently, the Th2-type cytokine IL-9 was identified by genetic mapping analyses as a key mediator that determines the susceptibility to asthma. This has been further supported by data from IL-9-transgenic mice in which the overexpression of IL-9 in the lung causes airway inflammation, mast cell hyperplasia, and bronchial hyperresponsiveness. In an accompanying paper, we demonstrate that murine bone marrow-derived mast cells (BMMC) after stimulation with either ionomycin, a combination of ionomycin and IL-1, or via IgE-Ag complexes and IL-1 are very potent producers of IL-9. Herein we show that a dramatic increase of IL-9 production is observed when BMMC activated with ionomycin/IL-1 or with IgE-Ag complexes/IL-1 are treated with either additional kit ligand (KL) or IL-10. Both KL and IL-10 considerably enhance the production of IL-9 mRNA and protein. We were also able to demonstrate that the production of endogenous IL-10 by activated mast cells acts on the production of IL-9. Half-life measurements of IL-9 mRNA revealed no significant effect by KL, but a 2-fold increase of mRNA stability under the influence of IL-10. Reporter gene assays of transfected BMMC showed an enhanced transcriptional activity of the IL-9 promoter in the presence of either IL-10 or KL compared with cells stimulated only with a combination of IL-1 and ionomycin. The influence of KL and IL-10 might be of physiological importance, because it is known that both cytokines are produced by bronchial epithelial cells.
Stassen
M
M
Institute of Immunology, Johannes Gutenberg University, Mainz, Germany.
Arnold
M
M
Hültner
L
L
Müller
C
C
Neudörfl
C
C
Reineke
T
T
Schmitt
E
E
D020121:5' Untranslated Regions / Q000502:physiology; D000276:Adjuvants, Immunologic / Q000502:physiology; D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology* / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000276:immunology; D007375:Interleukin-1 / Q000502:physiology*; D016753:Interleukin-10 / Q000502:physiology*; D016906:Interleukin-9 / Q000096:biosynthesis* / Q000235:genetics; D008407:Mast Cells / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000096:biosynthesis / Q000378:metabolism; D019089:Stem Cell Factor / Q000502:physiology*
D020121:5' Untranslated Regions; D000276:Adjuvants, Immunologic; D007375:Interleukin-1; D016906:Interleukin-9; D012333:RNA, Messenger; D019089:Stem Cell Factor; D016753:Interleukin-10