Accelerated apoptosis of lymphocytes by augmented induction of Bax in SSI-1 (STAT-induced STAT inhibitor-1) deficient mice.
Growth, differentiation, and programmed cell death (apoptosis) are mainly controlled by cytokines. The Janus kinase-signal transducers and activators of transcription (JAK-STAT) signal pathway is an important component of cytokine signaling. We have previously shown that STAT3 induces a molecule designated as SSI-1, which inhibits STAT3 functions. To clarify the physiological roles of SSI-1 in vivo, we generated, here, mice lacking SSI-1. These SSI-1-/- mice displayed growth retardation and died within 3 weeks after birth. Lymphocytes in the thymus and spleen of the SSI-1-/- mice exhibited accelerated apoptosis with aging, and their number was 20-25% of that in SSI-1+/+ mice at 10 days of age. However, the differentiation of lymphocytes lacking SSI-1 appeared to be normal. Among various pro- and anti-apoptotic molecules examined, an up-regulation of Bax was found in lymphocytes of the spleen and thymus of SSI-1-/- mice. These findings suggest that SSI-1 prevents apoptosis by inhibiting the expression of Bax.
Naka
T
T
Department of Medicine III, Osaka University Medical School, 2-2, Yamada-Oka, Suita, Osaka 565-0871, Japan.
Matsumoto
T
T
Narazaki
M
M
Fujimoto
M
M
Morita
Y
Y
Ohsawa
Y
Y
Saito
H
H
Nagasawa
T
T
Uchiyama
Y
Y
Kishimoto
T
T
D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D001854:Bone Marrow Cells / Q000276:immunology; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D002478:Cells, Cultured; D004791:Enzyme Inhibitors; D005434:Flow Cytometry; D015698:Genomic Library; D020287:In Situ Nick-End Labeling; D008214:Lymphocytes / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D019253:Proto-Oncogene Proteins c-bcl-2; D012097:Repressor Proteins; D013154:Spleen / Q000276:immunology; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D013601:T-Lymphocytes / Q000276:immunology* / Q000502:physiology; D013950:Thymus Gland / Q000276:immunology; D051028:bcl-2-Associated X Protein
C494827:Bax protein, mouse; D002352:Carrier Proteins; D004791:Enzyme Inhibitors; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012097:Repressor Proteins; C491590:Socs1 protein, mouse; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D051028:bcl-2-Associated X Protein; D011505:Protein-Tyrosine Kinases