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SOCS-1 is a central mediator of steroid-increased thymocyte apoptosis and decreased survival following sepsis

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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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Acknowledgments

This work was supported by NIH R01-GM46354, NIH R01-GM53209 (A.A.) and the Lifespan Developmental Grants (C.C.).

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Authors and Affiliations

  1. Division of Surgical Research, Department of surgery, Aldrich 227, Brown University School Medicine/Rhode Island Hospital,, 593 Eddy Street, Providence, RI, 02903, USA

    Chun-Shiang Chung, Yaping Chen, Patricia S. Grutkoski & Alfred Ayala

  2. Division of Critical Care, Cincinnati Children’s Hospital, Cincinnati, OH, 45229, USA

    Lesley Doughty

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  1. Chun-Shiang Chung
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  2. Yaping Chen
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Correspondence to Alfred Ayala.

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Chung, CS., Chen, Y., Grutkoski, P.S. et al. SOCS-1 is a central mediator of steroid-increased thymocyte apoptosis and decreased survival following sepsis. Apoptosis 12, 1143–1153 (2007). https://doi.org/10.1007/s10495-007-0059-7

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