Reduced kinase inhibitory region containing suppressor of cytokine signaling molecule levels in SLE patients is correlated to enhanced STAT1 activation (HUM3P.242)
| Autor: | BhagyaLaxmi Sukka-Ganesh, Tenisha Wilson, Reeves Westley, Howard Johnson, Joseph Larkin |
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| Rok vydání: | 2015 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 194:121.2-121.2 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.194.supp.121.2 |
| Popis: | Systemic Lupus erythematosus (SLE) is a chronic inflammatory autoimmune disorder with unknown etiology. Given the importance of the suppressor of cytokine signaling (SOCS) family of intracellular proteins in the regulation of lupus promoting cytokine signaling, we tested the hypothesis that SOCS deficiencies would be present in SLE patients. We therefore compared a group of 34 SLE patients, by disease activity (SLEDIA) and prednisone treatment, to 11 healthy controls for the presence of the kinase inhibitory region (KIR) bearing SOCS1 and SOCS3. We found that protein and mRNA levels of SOCS1 and SOCS3 were significantly reduced in PMBC’s isolated from SLE patients compared to controls. Further, decreased SOCS1, but not SOCS3 protein levels in the SLE patients was inversely correlated to pSTAT1 activation, but not Erk 1/2 or Akt. Notably, the inverted SOCS1/pSTAT1 ratio correlated to significantly enhanced MHC class II levels amongst SLE patients. Together these data suggest that SOCS1 deficiencies may play an essential role in the onset/progression of SLE in a subset of SLE patients, possibly through dysregulated STAT1 mediated antigen presentation. These studies represent a critical first step in implicating a role of SOCS1 and SOCS3 deficiencies in the progression of human SLE. Moreover, these studies point to the possibility that peptides, which partially mimic SOCS signaling and inhibit rodent autoimmune disease, may have efficacy in the treatment of human SLE. |
| Databáze: | OpenAIRE |
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