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 imm unity. Herein we report that in primary murine bone marrow-derived mast cel ls 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-hypor esponsive mouse strain BALB/c-LPSd, although in these cells the proinflamma tory 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. Co activation of mast cells with LPS leads to a synergistic activation of NF-k appaB, which is shown by an NF-kappaB-driven reporter gene construct. In th e presence of an inhibitor of NF-kappaB activation, the production of IL-9 is strongly decreased, whereas the expression of IL-13 is hardly reduced, a nd that of IL-4 is not affected at all. NF-kappaB drives the expression of IL-9 via three NF-kappaB binding sites within the IL-9 promoter, which we c haracterize 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 produ ction in the course of inflammatory reactions and allergic diseases.