Suppressors of cytokine signaling (SOCS) proteins in inflammatory bone disorders

Bone ◽  
2020 ◽  
Vol 140 ◽  
pp. 115538
Author(s):  
Mariana Rates Gonzaga Santos ◽  
Celso M. Queiroz-Junior ◽  
Mila Fernandes Moreira Madeira ◽  
Fabiana Simão Machado
2011 ◽  
Vol 2011 ◽  
pp. 1-11 ◽  
Author(s):  
Esther López ◽  
María Paz Zafra ◽  
Beatriz Sastre ◽  
Cristina Gámez ◽  
Mar Fernández-Nieto ◽  
...  

Asthma and nonasthmatic eosinophilic bronchitis (NAEB) are respiratory disorders characterized by a predominance of Th2 cells and eosinophilic inflammation. Suppressors of cytokine signaling (SOCS) proteins play an important role in Th2-mediated allergic responses through control of the balance between Th1 and Th2 cells, particularly, SOCS3 and SOCS5. The aim of this study was to analyze SOCS expression in human peripheral blood eosinophils from patients with asthma, NAEB and healthy controls. SOCS expression in eosinophils from subjects was demonstrated by different techniques. Results showed that expression of SOCS3 in eosinophils and CD4 T cells from patients was higher than in healthy subjects. In addition, we demonstrated that prostaglandin E2(PGE2) and Th2 cytokines are able to upregulate SOCS3 production in eosinophils and attenuate its degranulation. In conclusion, eosinophils are able to transcribe and translate SOCS3 protein and can contribute to the regulation of the Th1/Th2 balance through SOCS3 production.


2011 ◽  
Vol 31 (5) ◽  
pp. 980-985 ◽  
Author(s):  
Taiga Tamiya ◽  
Ikko Kashiwagi ◽  
Reiko Takahashi ◽  
Hideo Yasukawa ◽  
Akihiko Yoshimura

2013 ◽  
Vol 289 (2) ◽  
pp. 1092-1105 ◽  
Author(s):  
Supriya Srivastav ◽  
Writoban Basu Ball ◽  
Purnima Gupta ◽  
Jayeeta Giri ◽  
Anindita Ukil ◽  
...  

2005 ◽  
Vol 35 (1) ◽  
pp. 165-175 ◽  
Author(s):  
M Blumenstein ◽  
J A Keelan ◽  
J M Bowen-Shauver ◽  
M D Mitchell

Decreased suppressors of cytokine signaling (SOCS) activity in human gestational tissues may play a part in the onset/progression of term labor. Since SOCS proteins negatively regulate cytokine-mediated inflammatory processes, we hypothesized that SOCS proteins are elevated in gestational tissues from spontaneous preterm deliveries with intrauterine infection. SOCS1, −2 and −3 mRNAs and proteins were detectable by RT-PCR and immunoblotting respectively, in preterm amnion, choriodecidua and placenta, irrespective of infection status. Immunoperoxidase staining localized SOCS1, −2 and −3 to all cell types of the gestational membranes, with infiltrating leukocytes reacting strongly in infected tissues. In villous placenta, SOCS was immunolocalized to the syncytiotrophoblast with marked staining of round mesenchymal cells, possibly Hofbauer cells. Nuclear SOCS staining was seen in amnion, chorion and placental syncytiotrophoblasts. SOCS proteins were, in general, significantly more abundant in placenta compared with amnion or choriodecidua. Placental SOCS1 and interleukin-1β concentrations were positively correlated (r2=0.47; P<0.05). However, no changes in SOCS levels in any tissues were observed with intrauterine infection. The relatively large amounts of SOCS proteins in the placenta may reflect a placenta-specific immunoprotective response to minimize the elaboration and effects of cytokines with potential to harm the placenta and fetus. Lack of labor-associated changes in SOCS levels suggests that the regulation of SOCS expression in preterm gestational tissues differs from those at term, perhaps reflecting roles in regulating placental somatotropic responses.


2006 ◽  
Vol 282 (7) ◽  
pp. 4728-4737 ◽  
Author(s):  
Marlyse A. Debrincat ◽  
Jian-Guo Zhang ◽  
Tracy A. Willson ◽  
John Silke ◽  
Lisa M. Connolly ◽  
...  

The suppressors of cytokine signaling (SOCS) proteins inhibit cytokine action by direct interaction with Janus kinases or activated cytokine receptors. In addition to the N-terminal and Src homology 2 domains that mediate these interactions, SOCS proteins contain a C-terminal SOCS box. DNA data base searches have identified a number of other protein families that possess a SOCS box, of which the ankyrin repeat and SOCS box-containing (Asb) proteins constitute the largest. Although it is known that the SOCS proteins are involved in the negative regulation of cytokine signaling, the biological and biochemical functions of the Asbs are largely undefined. Using a proteomics approach, we demonstrate that creatine kinase B (CKB) interacts with Asb-9 in a specific, SOCS box-independent manner. This interaction increases the polyubiquitylation of CKB and decreases total CKB levels within the cell. The targeting of CKB for degradation by Asb-9 was primarily SOCS box-dependent and suggests that Asb-9 acts as a specific ubiquitin ligase regulating levels of this evolutionarily conserved enzyme.


2000 ◽  
Vol 113 (16) ◽  
pp. 2813-2819 ◽  
Author(s):  
D.L. Krebs ◽  
D.J. Hilton

Cytokines regulate cellular behavior by interacting with receptors on the plasma membrane of target cells and activating intracellular signal transduction cascades such as the JAK-STAT pathway. Suppressors of cytokine signaling (SOCS) proteins negatively regulate cytokine signaling. The SOCS family consists of eight proteins: SOCS1-SOCS7 and CIS, each of which contains a central Src-homology 2 (SH2) domain and a C-terminal SOCS box. The expression of CIS, SOCS1, SOCS2 and SOCS3 is induced in response to stimulation by a wide variety of cytokines, and overexpression of these proteins in cell lines results in inhibition of cytokine signaling. Thus, SOCS proteins appear to form part of a classical negative feedback loop. The analysis of mice lacking SOCS1 has revealed that it is critical in the negative regulation of IFN(gamma) signaling and in the differentiation of T cells. Additionally, the analysis of mouse embryos lacking SOCS3 suggests that SOCS3 negatively regulates fetal liver erythropoiesis, probably through its ability to modulate erythropoietin (Epo) signaling. Thus, the use of gene targeting has confirmed that SOCS proteins regulate cytokine signaling in a physiological setting.


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