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Sjögren's syndrome (SS) is a chronic autoimmune disease characterized by salivary and lacrimal gland dysfunction. Clinical observations and results from animal models of SS support the role of aberrant epithelial cell apoptosis and immune homeostasis loss in the glands as triggering factors for the autoimmune response. Vasoactive intestinal peptide (VIP) promotes potent anti-inflammatory effects in several inflammatory and autoimmune disease models, including the non-obese diabetic (NOD) mouse model of SS. With the knowledge that VIP modulates monocyte function through vasoactive intestinal peptide receptors (VPAC) and that immune homeostasis maintenance depends strongly upon a rapid and immunosuppressant apoptotic cell clearance by monocytes/macrophages, in this study we explored VPAC expression on monocytes from primary SS (pSS) patients and the ability of VIP to modulate apoptotic cell phagocytic function and cytokine profile. Monocytes isolated from individual pSS patients showed an increased expression of VPAC2 subtype of VIP receptors, absent in monocytes from control subjects, with no changes in VPAC1 expression. VPAC2 receptor expression could be induced further with lipopolysaccharide (LPS) in pSS monocytes and VIP inhibited the effect. Moreover, monocytes from pSS patients showed an impaired phagocytosis of apoptotic epithelial cells, as evidenced by reduced engulfment ability and the failure to promote an immunosuppressant cytokine profile. However, VIP neither modulated monocyte/macrophage phagocytic function nor did it reverse their inflammatory profile. We conclude that monocytes from pSS patients express high levels of VPAC2 and display a deficient clearance of apoptotic cells that is not modulated by VIP. © 2014 British Society for Immunology.


Documento: Artículo
Título:Monocytes from Sjögren's syndrome patients display increased vasoactive intestinal peptide receptor 2 expression and impaired apoptotic cell phagocytosis
Autor:Hauk, V.; Fraccaroli, L.; Grasso, E.; Eimon, A.; Ramhorst, R.; Hubscher, O.; Pérez Leirós, C.
Filiación:Laboratory of Immunopharmacology, Department of Biological Chemistry, School of Sciences, University of Buenos Aires - IQUIBICEN-CONICET, Buenos Aires, Argentina
Rheumatology Unit, Department of Medicine, CEMIC, Buenos Aires, Argentina
Palabras clave:Apoptotic cell clearance; Monocytes; Sjögren's syndrome patients; VPAC receptors; hydroxychloroquine; levothyroxine; lipopolysaccharide; pilocarpine; prednisone; vasoactive intestinal polypeptide receptor 1; vasoactive intestinal polypeptide receptor 2; adult; aged; apoptosis; article; cell function; cell isolation; cell phagocytosis; clinical article; controlled study; epithelium cell; female; human; human cell; immunomodulation; macrophage; monocyte; priority journal; protein expression; protein function; Sjoegren syndrome; systemic therapy; apoptotic cell clearance; monocytes; Sjögren's syndrome patients; VPAC receptors; Adult; Aged; Apoptosis; Case-Control Studies; Cytophagocytosis; Gene Expression Regulation; Humans; Lipopolysaccharides; Middle Aged; Monocytes; Receptors, Vasoactive Intestinal Peptide; Receptors, Vasoactive Intestinal Peptide, Type II; Sjogren's Syndrome; Vasoactive Intestinal Peptide; Young Adult
Página de inicio:662
Página de fin:670
Título revista:Clinical and Experimental Immunology
Título revista abreviado:Clin. Exp. Immunol.
CAS:hydroxychloroquine, 118-42-3, 525-31-5; levothyroxine, 51-48-9; pilocarpine, 148-72-1, 54-71-7, 92-13-7; prednisone, 53-03-2


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---------- APA ----------
Hauk, V., Fraccaroli, L., Grasso, E., Eimon, A., Ramhorst, R., Hubscher, O. & Pérez Leirós, C. (2014) . Monocytes from Sjögren's syndrome patients display increased vasoactive intestinal peptide receptor 2 expression and impaired apoptotic cell phagocytosis. Clinical and Experimental Immunology, 177(3), 662-670.
---------- CHICAGO ----------
Hauk, V., Fraccaroli, L., Grasso, E., Eimon, A., Ramhorst, R., Hubscher, O., et al. "Monocytes from Sjögren's syndrome patients display increased vasoactive intestinal peptide receptor 2 expression and impaired apoptotic cell phagocytosis" . Clinical and Experimental Immunology 177, no. 3 (2014) : 662-670.
---------- MLA ----------
Hauk, V., Fraccaroli, L., Grasso, E., Eimon, A., Ramhorst, R., Hubscher, O., et al. "Monocytes from Sjögren's syndrome patients display increased vasoactive intestinal peptide receptor 2 expression and impaired apoptotic cell phagocytosis" . Clinical and Experimental Immunology, vol. 177, no. 3, 2014, pp. 662-670.
---------- VANCOUVER ----------
Hauk, V., Fraccaroli, L., Grasso, E., Eimon, A., Ramhorst, R., Hubscher, O., et al. Monocytes from Sjögren's syndrome patients display increased vasoactive intestinal peptide receptor 2 expression and impaired apoptotic cell phagocytosis. Clin. Exp. Immunol. 2014;177(3):662-670.