IL-9 and IL-13 production by activated mast cells is strongly enhanced in the presence of lipopolysaccharide: NF-kappa B is decisively involved in the expression of IL-9.
Mast cells, due to their ability to produce a large panel of mediators and cytokines, participate in a variety of processes in adaptive and innate immunity. Herein we report that in primary murine bone marrow-derived mast cells activated with ionomycin or IgE-Ag the bacterial endotoxin LPS strongly enhances the expression of IL-9 and IL-13, but not IL-4. This costimulatory effect of LPS is absent in activated mast cells derived from the LPS-hyporesponsive mouse strain BALB/c-LPS(d), although in these cells the proinflammatory cytokine IL-1 can still substitute for LPS. The enhanced production of mast cell-derived IL-13 in the presence of IL-1 is a novel observation. Coactivation of mast cells with LPS leads to a synergistic activation of NF-kappa B, which is shown by an NF-kappa B-driven reporter gene construct. In the presence of an inhibitor of NF-kappa B activation, the production of IL-9 is strongly decreased, whereas the expression of IL-13 is hardly reduced, and that of IL-4 is not affected at all. NF-kappa B drives the expression of IL-9 via three NF-kappa B binding sites within the IL-9 promoter, which we characterize using gel shift analyses and reporter gene assays. In the light of recent reports that strongly support critical roles for IL-9 and IL-13 in allergic lung inflammation, our results emphasize the potential clinical importance of LPS as an enhancer of mast cell-derived IL-9 and IL-13 production in the course of inflammatory reactions and allergic diseases.
Institute of Immunology, Johannes Gutenberg University, Mainz, Germany.
M
M
Stassen
C
C
Müller
M
M
Arnold
L
L
Hültner
S
S
Klein-Hessling
C
C
Neudörfl
T
T
Reineke
E
E
Serfling
E
E
Schmitt
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D001665:Binding Sites / Q000235:genetics / Q000276:immunology; D001854:Bone Marrow Cells / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000276:immunology; D018793:Interleukin-13 / Q000096:biosynthesis*; D016906:Interleukin-9 / Q000096:biosynthesis* / Q000235:genetics; D008070:Lipopolysaccharides / Q000276:immunology* / Q000494:pharmacology; D008407:Mast Cells / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D020297:Mice, Congenic; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D011401:Promoter Regions, Genetic / Q000276:immunology; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology
D000276:Adjuvants, Immunologic; D018793:Interleukin-13; D016906:Interleukin-9; D008070:Lipopolysaccharides; D016328:NF-kappa B