Interleukin-15 prevents mouse mast cell apoptosis through STAT6-mediated Bcl-x(L) expression

Interleukin (IL)-15 is a member of the cytokine family with T and natural k iller (NK) cell growth-promoting activity. In mast cells, however, IL-15 us es a distinct receptor system different from that used in T and NK cells. W e 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 th e present study, we have demonstrated that IL-15 prevents MC/9 and bone mar row-derived mast cell apoptosis induced by factor withdrawal or anti-Fas an tibody treatment, IL-15 increased mRNA and protein levels of an anti-apopto tic protein (Bcl-x(L)) in these cells, whereas bcl-2 mRNA remained unchange d. In addition, the transcriptional activity of the bcl-x(L), promoter was increased by IL-15 in MC/9 eels. 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 S TAT6 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 tha t IL-15 plays an important role in maintaining the number of mast cells thr ough Bcl-xL expression mediated by STAT6.