Co-culture system of human salivary gland epithelial cells and immune cells from primary Sjögren's syndrome patients: an in vitro approach to study the effects of Rituximab on the activation of the Raf-1/ERK1/2 pathway.
Primary Sjögren's syndrome (pSS) is a chronic autoimmune disorder of the exocrine glands with associated lymphocytic infiltrates in the affected glands. Dryness of the mouth and eyes results from involvement of the salivary and lacrimal glands. The efficacy of Rituximab (RTX) in pSS is still open to debate. This study delineates the signaling pathway involved in RTX-mediated down-regulation of pro-inflammatory factors in a co-culture system of pSS salivary gland epithelial cells (SGEC) with syngeneic pSS B-lymphocytes. In addition, the effects of RTX on the activation of the Raf-1/ERK1/2 pathway in pSS SGEC co-cultured with syngeneic pSS T-lymphocytes were also investigated. This study demonstrated that RTX may interfere with the ERK1/2 pathway in a syngeneic co-culture of pSS SGEC with pSS B-lymphocytes, leading to decreased cytokine production by SGEC. These novel findings reveal that syngeneic co-culture of pSS SGEC with pSS B-lymphocytes leads to a down-regulation of Raf-1 in epithelial cells that adversely regulates the activity of the ERK1/2 pathway and determines a subsequent reduction of the release of pro-inflammatory factors.
Department of Basic Medical Sciences, Section of Human Anatomy and Histology, Laboratory of Cell Biology, University of Bari Medical School, Bari 70124, Italy.
Sabrina
S
Lisi
Department of Basic Medical Sciences, Section of Human Anatomy and Histology, Laboratory of Cell Biology, University of Bari Medical School, Bari 70124, Italy.
Margherita
M
Sisto
Interdisciplinary Department of Medicine, Section of Rheumatology, University of Bari Medical School, Bari 70124, Italy.
Massimo
M
D'Amore
Department of Biological and Environmental Sciences and Technologies, University of Salento, Lecce 73100, Italy.
Dario Domenico
DD
Lofrumento
D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology; D018836:Inflammation Mediators / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D019908:Proto-Oncogene Proteins c-raf / Q000096:biosynthesis / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D000069283:Rituximab / Q000494:pharmacology*; D012469:Salivary Glands / Q000166:cytology / Q000276:immunology*; D012859:Sjogren's Syndrome / Q000188:drug therapy / Q000473:pathology*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology
D016207:Cytokines; D005419:Flavonoids; D018836:Inflammation Mediators; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D000069283:Rituximab; D019908:Proto-Oncogene Proteins c-raf; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one
ERK; Raf-1; Rituximab; Sjögren’s syndrome; cytokines