Interleukin-15 prevents mouse mast cell apoptosis through STAT6-mediated Bcl-xL expression

Interleukin (IL)-15 is a member of the cytokine family with T and natural killer (NK) cell growth-promoting activity. In mast cells, however, IL-15 uses a distinct receptor system different from that used in T and NK cells. We recently reported that IL-15 induces STAT6 activation and IL-4 production in a mouse mast cell line (MC/9) and bone marrow-derived mast cells. In the present study, we have demonstrated that IL-15 prevents MC/9 and bone marrow-derived mast cell apoptosis induced by factor withdrawal or anti-Fas antibody treatment. IL-15 increased mRNA and protein levels of an anti-apoptotic protein (Bcl-x(L)) in these cells, whereas bcl-2 mRNA remained unchanged. In addition, the transcriptional activity of the bcl-x(L) promoter was increased by IL-15 in MC/9 cells. In an electrophoretic mobility shift assay, IL-15 induced STAT6 binding to the STAT recognition site in the bcl-x(L) gene promoter. Furthermore, the expression of a dominant-negative form of STAT6 abrogated the effects of IL-15 on both bcl-x(L) mRNA up-regulation and prevention of apoptosis in mast cells. Altogether, our results suggest that IL-15 plays an important role in maintaining the number of mast cells through Bcl-x(L) expression mediated by STAT6.