title: Rituximab-mediated Raf kinase inhibitor protein induction modulates NF-κB in Sjögren syndrome.
abstract: 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-κB) DNA binding assays were used as methods. Supporting the benefits of RTX, this study demonstrates that RTX decreases NF-κB activity and interrupts the NF-κB 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-κB activation in pSS salivary gland epithelial cells.
authors.affiliation: Department of Basic Medical Sciences, Neurosciences and Sense Organs, Human Anatomy and Histology Section, Laboratory of Cell Biology, University of Bari Medical School, Bari, Italy.
authors.forename: Margherita
authors.initials: M
authors.lastname: Sisto
authors.forename: Sabrina
authors.initials: S
authors.lastname: Lisi
authors.forename: Massimo
authors.initials: M
authors.lastname: D'Amore
authors.forename: Dario D
authors.initials: DD
authors.lastname: Lofrumento
mesh_terms: D058846:Antibodies, Monoclonal, Murine-Derived / Q000494:pharmacology*; D015153:Blotting, Western; D002478:Cells, Cultured; D018920:Coculture Techniques; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology*; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D049488:Phosphatidylethanolamine Binding Protein / Q000378:metabolism*; D034741:RNA, Small Interfering; D060888:Real-Time Polymerase Chain Reaction; D000069283:Rituximab; D012469:Salivary Glands / Q000187:drug effects / Q000378:metabolism; D012859:Sjogren's Syndrome / Q000378:metabolism*; D059467:Transcriptome / Q000187:drug effects; D014162:Transfection
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D007155:Immunologic Factors; D016328:NF-kappa B; C511482:PEBP1 protein, human; D049488:Phosphatidylethanolamine Binding Protein; D034741:RNA, Small Interfering; D000069283:Rituximab
keywords: Raf-1 kinase inhibitor protein; Rituximab; Sjögren syndrome; array; nuclear factor-κB