Rituximab-mediated Raf kinase inhibitor protein induction modulates NF-κB in Sjögren's syndrome

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.


Tutti gli autori

  • SISTO M.;LISI S.

Titolo volume/Rivista

Non Disponibile


Anno di pubblicazione

2014

ISSN

1365-2567

ISBN

Non Disponibile


Numero di citazioni Wos

6

Ultimo Aggiornamento Citazioni

Non Disponibile


Numero di citazioni Scopus

6

Ultimo Aggiornamento Citazioni

Non Disponibile


Settori ERC

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Codici ASJC

Non Disponibile