Suppressor of cytokine signaling 3 (SOCS3) is a negative regulator of granulocyte-colony stimulating factor (G-CSF) signaling in vivo. SOCS proteins regulate cytokine signaling by binding, via their SH2 domains, to activated cytokine receptors or their associated Janus kinases. In addition, they bind to the elongin B/C ubiquitin ligase complex via the SOCS box. To ascertain the contribution of the SOCS box of SOCS3 to in vivo regulation of G-CSF signaling, we generated mice expressing a truncated SOCS3 protein lacking the C-terminal SOCS box (SOCS3ΔSB/ΔSB). SOCS3 ΔSB/ΔSB mice were viable, had normal steady-state hematopoiesis, and did not develop inflammatory disease. Despite the mild phenotype, STAT3 activation in response to G-CSF signaling was prolonged in SOCS3ΔSB/ΔSB bone marrow. SOCS3 ΔSB/ΔSB bone marrow contained increased numbers of colony-forming cells responsive to G-CSF and IL-6. Treatment of the mice with pharmacologic doses of G-CSF, which mimics emergency granulopoiesis and therapeutic use of G-CSF, revealed that SOCS3ΔSB/ΔSB mice were hyperresponsive to G-CSF. Compared with wild-type mice, SOCS3 ΔSB/ΔSB mice developed a more florid arthritis when tested using an acute disease model. Overall, the results establish a role for the SOCS box of SOCS3 in the in vivo regulation of G-CSF signaling and the response to inflammatory stimuli.

WHO Classification and WPSS Score Predict Post-Transplant Outcome in Adults with Myelodysplastic Syndrome : A Retrospective Study by GITMO - Gruppo Italiano Trapianto Midollo Osseo / P.E. Alessandrino, M.G. Della Porta, A. Bacigalupo, M.T. Van Lint, M. Falda, F. Onida, M. Bernardi, A.P. Iori, A. Rambaldi, R. Cerretti, P. Marenco, P. Pioltelli, C. Pascutto, R. Oneto, R. Fanin, A. Bosi. - In: BLOOD. - ISSN 0006-4971. - 110:11(2007), pp. 1466-1466. ((Intervento presentato al 50. convegno ASH Annual Meeting tenutosi a San Francisco, CA, USA nel 2008.

WHO Classification and WPSS Score Predict Post-Transplant Outcome in Adults with Myelodysplastic Syndrome : A Retrospective Study by GITMO - Gruppo Italiano Trapianto Midollo Osseo

F. Onida;A. Rambaldi;
2007

Abstract

Suppressor of cytokine signaling 3 (SOCS3) is a negative regulator of granulocyte-colony stimulating factor (G-CSF) signaling in vivo. SOCS proteins regulate cytokine signaling by binding, via their SH2 domains, to activated cytokine receptors or their associated Janus kinases. In addition, they bind to the elongin B/C ubiquitin ligase complex via the SOCS box. To ascertain the contribution of the SOCS box of SOCS3 to in vivo regulation of G-CSF signaling, we generated mice expressing a truncated SOCS3 protein lacking the C-terminal SOCS box (SOCS3ΔSB/ΔSB). SOCS3 ΔSB/ΔSB mice were viable, had normal steady-state hematopoiesis, and did not develop inflammatory disease. Despite the mild phenotype, STAT3 activation in response to G-CSF signaling was prolonged in SOCS3ΔSB/ΔSB bone marrow. SOCS3 ΔSB/ΔSB bone marrow contained increased numbers of colony-forming cells responsive to G-CSF and IL-6. Treatment of the mice with pharmacologic doses of G-CSF, which mimics emergency granulopoiesis and therapeutic use of G-CSF, revealed that SOCS3ΔSB/ΔSB mice were hyperresponsive to G-CSF. Compared with wild-type mice, SOCS3 ΔSB/ΔSB mice developed a more florid arthritis when tested using an acute disease model. Overall, the results establish a role for the SOCS box of SOCS3 in the in vivo regulation of G-CSF signaling and the response to inflammatory stimuli.
Settore MED/15 - Malattie del Sangue
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/55908
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