SOCS-1 is a central mediator of steroid-increased thymocyte apoptosis and decreased survival following sepsis |
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Authors: | Chun-Shiang Chung Yaping Chen Patricia S Grutkoski Lesley Doughty Alfred Ayala |
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Institution: | (1) Division of Surgical Research, Department of surgery, Aldrich 227, Brown University School Medicine/Rhode Island Hospital,, 593 Eddy Street, Providence, RI 02903, USA;(2) Division of Critical Care, Cincinnati Children’s Hospital, Cincinnati, OH 45229, USA |
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Abstract: | Suppressor of Cytokine Signaling (SOCS) proteins are recently identified inhibitors/regulators of cytokine/growth factor signaling
pathways. We have previously shown that SOCS-3 is upregulated in mice after sepsis induced by cecal ligation and puncture;
however, the contribution of SOCS-1 to septic morbidity and mortality is unclear. In the present study, we characterized SOCS-1
expression in different tissues and delineated putative mechanisms effecting SOCS-1 expression in thymus from septic mice.
We observed no difference in SOCS-1 expression in blood, peritoneal leukocytes, lung, and spleen taken from sham or septic
animals at 24 h after surgery. In contrast, SOCS-1 expression in thymus declined significantly after sepsis and this down-regulation
of SOCS-1 was associated with increased thymocyte apoptosis as well as augmented Bax recruitment to the mitochondria. Administration
of RU-38486, a steroid receptor antagonist, reversed the above effects in the septic thymus. Furthermore, SOCS-1+/− mice showed
a significant higher mortality when compared to SOCS-1+/+ mice after sepsis. Together, these results show that sepsis increases
steroid-induced thymic lymphoid cell apoptosis, which is associated with reduced SOCS-1 expression and increased Bax translocation
to mitochondria. Survival data suggests that SOCS-1 protein may play an important role in sepsis. |
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Keywords: | Bax Dexamethasone RU-38486 STAT-1 TLR4 |
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