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10.1111/sji.12475

http://scihub22266oqcxt.onion/10.1111/sji.12475
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C5131794!5131794!27781323
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suck abstract from ncbi


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pmid27781323      Scand+J+Immunol 2016 ; 84 (5): 299-309
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  • Therapeutic Potential for Targeting the Suppressor of Cytokine Signaling-1 pathway for the treatment of SLE #MMPMID27781323
  • Sukka-Ganesh B; Larkin J
  • Scand J Immunol 2016[Nov]; 84 (5): 299-309 PMID27781323show ga
  • Although the specific events dictating systemic lupus erythematosus (SLE) pathology remain unclear, abundant evidence indicates a critical role for dysregulated cytokine signaling in disease progression. Notably, the suppressor of cytokine signaling (SOCS) family of intracellular proteins, in particular the kinase inhibitory region (KIR) bearing SOCS1 and SOCS3, play a critical role in regulating cytokine signaling. To assess a relationship between SOCS1/SOCS3 expression and SLE, the goals of this study were to: 1) evaluate the time kinetics of SOCS1/SOCS3 message and protein expression based on SLE associated stimulations, 2) compare levels of SOCS1 and SOCS3 present in SLE patients and healthy controls by message and protein, 3) relate SOCS1/SOCS3 expression to inflammatory markers in SLE patients, and 4) correlate SOCS1/SOCS3 levels to current treatments. We found that SOCS1 and SOCS3 were most abundant in murine splenic samples at 48 hours subsequent to stimulation by anti-CD3, LPS, or interferon gamma. In addition, significant reductions in SOCS1 and SOCS3 were present within PMBC?s of SLE patients compared to controls by both mRNA and protein expression. We also found that decreased levels of SOCS1 in SLE patients were correlated to enhanced levels of inflammatory markers and up-regulated expression of MHC class II. Finally, we show that patients receiving steroid treatment possessed higher levels SOCS1 compared to SLE patient counterparts, and that steroid administration to human PBMCs up-regulated SOCS1 message in a dose and time dependent manner. Together, these results suggest that therapeutic strategies focused on SOCS1 signaling may have efficacy in the treatment of SLE.
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