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Rituximab‐mediated Raf kinase inhibitor protein induction modulates NF‐ κ B in Sjögren syndrome
Author(s) -
Sisto Margherita,
Lisi Sabrina,
D'Amore Massimo,
Lofrumento Dario D.
Publication year - 2014
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.12288
Subject(s) - gene silencing , western blot , nf κb , small interfering rna , cancer research , transfection , blot , flow cytometry , kinase , signal transduction , iκbα , salivary gland , biology , inflammation , microbiology and biotechnology , gene , immunology , biochemistry
Summary Primary Sjögren syndrome (pSS) is an autoimmune disorder characterized by an epithelial injury surrounded by dense lymphocytic infiltrates. The conditions for the long‐term maintenance of human salivary gland epithelial cells 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 protein array analysis, Western blot, flow cytometry, small interfering RNA transfection and nuclear factor‐κB (NF‐ κ B) DNA binding assays were used as methods. Supporting the benefits of RTX, this study demonstrates that RTX decreases NF‐ κ B activity and interrupts the NF‐ κ B signalling pathway through the up‐regulation of the Raf‐1 kinase inhibitor protein (RKIP). Over‐expression of RKIP down‐regulates interleukins, their receptors and the expression of genes encodes proteins that attracted lymphocytes. Silencing of the RKIP gene leads to significantly increased expression and release of pro‐inflammatory mediators supporting that RKIP expression could be involved in the suppression of NF‐ κ B activation in pSS salivary gland epithelial cells.