Monocytes from Sjögren's syndrome patients display increased vasoactive intestinal peptide receptor 2 expression and impaired apoptotic cell phagocytosis
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...
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todo:paper_00099104_v177_n3_p662_Hauk2023-10-03T14:08:49Z Monocytes from Sjögren's syndrome patients display increased vasoactive intestinal peptide receptor 2 expression and impaired apoptotic cell phagocytosis Hauk, V. Fraccaroli, L. Grasso, E. Eimon, A. Ramhorst, R. Hubscher, O. Pérez Leirós, C. 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 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. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_00099104_v177_n3_p662_Hauk |
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Universidad de Buenos Aires |
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I-28 |
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R-134 |
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Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
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 |
| spellingShingle |
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 Hauk, V. Fraccaroli, L. Grasso, E. Eimon, A. Ramhorst, R. Hubscher, O. Pérez Leirós, C. Monocytes from Sjögren's syndrome patients display increased vasoactive intestinal peptide receptor 2 expression and impaired apoptotic cell phagocytosis |
| topic_facet |
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 |
| description |
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. |
| format |
JOUR |
| author |
Hauk, V. Fraccaroli, L. Grasso, E. Eimon, A. Ramhorst, R. Hubscher, O. Pérez Leirós, C. |
| author_facet |
Hauk, V. Fraccaroli, L. Grasso, E. Eimon, A. Ramhorst, R. Hubscher, O. Pérez Leirós, C. |
| author_sort |
Hauk, V. |
| title |
Monocytes from Sjögren's syndrome patients display increased vasoactive intestinal peptide receptor 2 expression and impaired apoptotic cell phagocytosis |
| title_short |
Monocytes from Sjögren's syndrome patients display increased vasoactive intestinal peptide receptor 2 expression and impaired apoptotic cell phagocytosis |
| title_full |
Monocytes from Sjögren's syndrome patients display increased vasoactive intestinal peptide receptor 2 expression and impaired apoptotic cell phagocytosis |
| title_fullStr |
Monocytes from Sjögren's syndrome patients display increased vasoactive intestinal peptide receptor 2 expression and impaired apoptotic cell phagocytosis |
| title_full_unstemmed |
Monocytes from Sjögren's syndrome patients display increased vasoactive intestinal peptide receptor 2 expression and impaired apoptotic cell phagocytosis |
| title_sort |
monocytes from sjögren's syndrome patients display increased vasoactive intestinal peptide receptor 2 expression and impaired apoptotic cell phagocytosis |
| url |
http://hdl.handle.net/20.500.12110/paper_00099104_v177_n3_p662_Hauk |
| work_keys_str_mv |
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