Primary Sjögren's syndrome (pSS) is an autoimmune disorder characterized by an epithelium injury surrounded by dense lymphocytic infiltrates. The conditions for the long-term maintenance of human salivary gland epithelial cells (SGEC) from pSS patients, and a co-culture system with pSS lymphocytes were used to assess the effect of Rituximab (RTX) on the inflammatory condition and progression in pSS. Quantitative Real-Time PCR, genes and proteins Array analysis, Western blot, flow cytometry, siRNAs transfection and NF-kB DNA binding assays were used as methods. Supporting the RTX's benefits, this study demonstrates that RTX decreases NF-κB activity and interrupts NF-κB signalling pathway through the up-regulation of the Raf-1 kinase inhibitor protein (RKIP). RKIP overexpression down-regulates interleukins, their receptors and the expression of genes encodes proteins that attracted lymphocytes. RKIP gene silencing leads to significantly increased expression and/or release of pro-inflammatory mediators supporting that RKIP expression could be involved in the suppression of NF-κB activation in pSS SGEC.
Rituximab-mediated Raf kinase inhibitor protein induction modulates NF-κB in Sjögren's syndrome
SISTO, MARGHERITA;LISI, SABRINA;
2014-01-01
Abstract
Primary Sjögren's syndrome (pSS) is an autoimmune disorder characterized by an epithelium injury surrounded by dense lymphocytic infiltrates. The conditions for the long-term maintenance of human salivary gland epithelial cells (SGEC) from pSS patients, and a co-culture system with pSS lymphocytes were used to assess the effect of Rituximab (RTX) on the inflammatory condition and progression in pSS. Quantitative Real-Time PCR, genes and proteins Array analysis, Western blot, flow cytometry, siRNAs transfection and NF-kB DNA binding assays were used as methods. Supporting the RTX's benefits, this study demonstrates that RTX decreases NF-κB activity and interrupts NF-κB signalling pathway through the up-regulation of the Raf-1 kinase inhibitor protein (RKIP). RKIP overexpression down-regulates interleukins, their receptors and the expression of genes encodes proteins that attracted lymphocytes. RKIP gene silencing leads to significantly increased expression and/or release of pro-inflammatory mediators supporting that RKIP expression could be involved in the suppression of NF-κB activation in pSS SGEC.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
