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

• Published in: The Journal of immunology (1950) 2001-04, Vol.166 (7), p.4391-4398
• Main Authors: Stassen, M, Müller, C, Arnold, M, Hültner, L, Klein-Hessling, S, Neudörfl, C, Reineke, T, Serfling, E, Schmitt, E
• Format: Article
• Language: English
• Subjects: Adjuvants, Immunologic - pharmacology; Animals; Binding Sites - genetics; Binding Sites - immunology; Bone Marrow Cells - immunology; Bone Marrow Cells - metabolism; Cells, Cultured; Gene Expression Regulation - immunology; Interleukin-13 - biosynthesis; Interleukin-9 - biosynthesis; Interleukin-9 - genetics; Lipopolysaccharides - immunology; Lipopolysaccharides - pharmacology; Mast Cells - immunology; Mast Cells - metabolism; Mice; Mice, Congenic; Mice, Inbred BALB C; Mice, Inbred C3H; NF-kappa B - genetics; NF-kappa B - metabolism; NF-kappa B - physiology; Promoter Regions, Genetic - immunology; Signal Transduction - genetics; Signal Transduction - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.166.7.4391

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.