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 coculture 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 upregulation 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

  • M. Sisto , S. Lisi , M. D’Amore , D.D. Lofrumento

Titolo volume/Rivista

IMMUNOLOGY


Anno di pubblicazione

2014

ISSN

0019-2805

ISBN

Non Disponibile


Numero di citazioni Wos

5

Ultimo Aggiornamento Citazioni

25/04/2018


Numero di citazioni Scopus

5

Ultimo Aggiornamento Citazioni

26/04/2018


Settori ERC

Non Disponibile

Codici ASJC

Non Disponibile