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.
Masuda
A
A
Second Department of Internal Medicine, Nagoya University School of Medicine, Nagoya 466-8550, Japan.
Matsuguchi
T
T
Yamaki
K
K
Hayakawa
T
T
Yoshikai
Y
Y
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002460:Cell Line; D019409:Interleukin-15 / Q000494:pharmacology / Q000502:physiology*; D008407:Mast Cells / Q000473:pathology* / Q000502:physiology*; D051379:Mice; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000502:physiology*; D050800:STAT6 Transcription Factor; D015398:Signal Transduction / Q000187:drug effects; D015534:Trans-Activators / Q000502:physiology*; D051020:bcl-X Protein
C494812:Bcl2l1 protein, mouse; D019409:Interleukin-15; D019253:Proto-Oncogene Proteins c-bcl-2; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D015534:Trans-Activators; D051020:bcl-X Protein