Vasoactive intestinal peptide/vasoactive intestinal peptide receptor relative expression in salivary glands as one endogenous modulator of acinar cell apoptosis in a murine model of Sjögren's syndrome

Sjögren's syndrome (SS) is a chronic autoimmune disease characterized by a progressive oral and ocular dryness that correlates poorly with the autoimmune damage of the glands. It has been proposed that a loss of homeostatic equilibrium in the glands is partly responsible for salivary dysfunctio...

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Autores principales: Hauk, Vanesa Cintia, Calafat, Mario José, Larocca, Luciana, Fraccaroli, Laura Virginia, Grasso, Esteban Nicolás, Ramhorst, Rosanna Elizabeth, Pérez Leirós, Claudia
Publicado: 2011
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VIP
Acceso en línea:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00099104_v166_n3_p309_Hauk
http://hdl.handle.net/20.500.12110/paper_00099104_v166_n3_p309_Hauk
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spelling paper:paper_00099104_v166_n3_p309_Hauk2023-06-08T14:34:07Z Vasoactive intestinal peptide/vasoactive intestinal peptide receptor relative expression in salivary glands as one endogenous modulator of acinar cell apoptosis in a murine model of Sjögren's syndrome Hauk, Vanesa Cintia Calafat, Mario José Larocca, Luciana Fraccaroli, Laura Virginia Grasso, Esteban Nicolás Ramhorst, Rosanna Elizabeth Pérez Leirós, Claudia Acinar cell apoptosis and clearance Sjögren's syndrome VIP cyclic AMP cyclic AMP dependent protein kinase tumor necrosis factor alpha vasoactive intestinal polypeptide vasoactive intestinal polypeptide receptor 1 acinar cell animal cell animal experiment animal model animal tissue apoptosis article cell function cell isolation cell survival controlled study female homeostasis inflammation macrophage mouse nonhuman phagocytosis phenotype priority journal protein expression salivary gland Sjoegren syndrome submandibular gland Acinar Cells Animals Apoptosis Autoimmune Diseases Cell Survival Cells, Cultured Cyclic AMP Cyclic AMP-Dependent Protein Kinases Disease Models, Animal Macrophages Mice Mice, Inbred BALB C Mice, Inbred NOD NF-kappa B Phagocytosis Receptors, Vasoactive Intestinal Peptide Sjogren's Syndrome Submandibular Gland Tumor Necrosis Factor-alpha Vasoactive Intestinal Peptide Sjögren's syndrome (SS) is a chronic autoimmune disease characterized by a progressive oral and ocular dryness that correlates poorly with the autoimmune damage of the glands. It has been proposed that a loss of homeostatic equilibrium in the glands is partly responsible for salivary dysfunction with acinar cells involved actively in the pathogenesis of SS. The non-obese diabetic (NOD) mouse model of Sjögren's syndrome develops secretory dysfunction and early loss of glandular homeostatic mechanisms, with mild infiltration of the glands. Based on the vasodilator, prosecretory and trophic effects of the vasoactive intestinal peptide (VIP) on acini as well as its anti-inflammatory properties we hypothesized that the local expression of VIP/vasoactive intestinal peptide receptor (VPAC) system in salivary glands could have a role in acinar cell apoptosis and macrophage function thus influencing gland homeostasis. Here we show a progressive decline of VIP expression in submandibular glands of NOD mice with no changes in VPAC receptor expression compared with normal mice. The deep loss of endogenous VIP was associated with a loss of acinar cells through apoptotic mechanisms that could be induced further by tumour necrosis factor (TNF)-α and reversed by VIP through a cyclic adenosine-5'-monophosphate (cAMP)/protein kinase A (PKA)-mediated pathway. The clearance of apoptotic acinar cells by macrophages was impaired for NOD macrophages but a shift from inflammatory to regulatory phenotype was induced in macrophages during phagocytosis of apoptotic acinar cells. These results support that the decline in endogenous VIP/VPAC local levels might influence the survival/apoptosis intracellular set point in NOD acinar cells and their clearance, thus contributing to gland homeostasis loss. © 2011 The Authors. Clinical and Experimental Immunology © 2011 British Society for Immunology. Fil:Hauk, V. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Calafat, M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Larocca, L. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Fraccaroli, L. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Grasso, E. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Ramhorst, R. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Leirós, C.P. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2011 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00099104_v166_n3_p309_Hauk http://hdl.handle.net/20.500.12110/paper_00099104_v166_n3_p309_Hauk
institution Universidad de Buenos Aires
institution_str I-28
repository_str R-134
collection Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic Acinar cell apoptosis and clearance
Sjögren's syndrome
VIP
cyclic AMP
cyclic AMP dependent protein kinase
tumor necrosis factor alpha
vasoactive intestinal polypeptide
vasoactive intestinal polypeptide receptor 1
acinar cell
animal cell
animal experiment
animal model
animal tissue
apoptosis
article
cell function
cell isolation
cell survival
controlled study
female
homeostasis
inflammation
macrophage
mouse
nonhuman
phagocytosis
phenotype
priority journal
protein expression
salivary gland
Sjoegren syndrome
submandibular gland
Acinar Cells
Animals
Apoptosis
Autoimmune Diseases
Cell Survival
Cells, Cultured
Cyclic AMP
Cyclic AMP-Dependent Protein Kinases
Disease Models, Animal
Macrophages
Mice
Mice, Inbred BALB C
Mice, Inbred NOD
NF-kappa B
Phagocytosis
Receptors, Vasoactive Intestinal Peptide
Sjogren's Syndrome
Submandibular Gland
Tumor Necrosis Factor-alpha
Vasoactive Intestinal Peptide
spellingShingle Acinar cell apoptosis and clearance
Sjögren's syndrome
VIP
cyclic AMP
cyclic AMP dependent protein kinase
tumor necrosis factor alpha
vasoactive intestinal polypeptide
vasoactive intestinal polypeptide receptor 1
acinar cell
animal cell
animal experiment
animal model
animal tissue
apoptosis
article
cell function
cell isolation
cell survival
controlled study
female
homeostasis
inflammation
macrophage
mouse
nonhuman
phagocytosis
phenotype
priority journal
protein expression
salivary gland
Sjoegren syndrome
submandibular gland
Acinar Cells
Animals
Apoptosis
Autoimmune Diseases
Cell Survival
Cells, Cultured
Cyclic AMP
Cyclic AMP-Dependent Protein Kinases
Disease Models, Animal
Macrophages
Mice
Mice, Inbred BALB C
Mice, Inbred NOD
NF-kappa B
Phagocytosis
Receptors, Vasoactive Intestinal Peptide
Sjogren's Syndrome
Submandibular Gland
Tumor Necrosis Factor-alpha
Vasoactive Intestinal Peptide
Hauk, Vanesa Cintia
Calafat, Mario José
Larocca, Luciana
Fraccaroli, Laura Virginia
Grasso, Esteban Nicolás
Ramhorst, Rosanna Elizabeth
Pérez Leirós, Claudia
Vasoactive intestinal peptide/vasoactive intestinal peptide receptor relative expression in salivary glands as one endogenous modulator of acinar cell apoptosis in a murine model of Sjögren's syndrome
topic_facet Acinar cell apoptosis and clearance
Sjögren's syndrome
VIP
cyclic AMP
cyclic AMP dependent protein kinase
tumor necrosis factor alpha
vasoactive intestinal polypeptide
vasoactive intestinal polypeptide receptor 1
acinar cell
animal cell
animal experiment
animal model
animal tissue
apoptosis
article
cell function
cell isolation
cell survival
controlled study
female
homeostasis
inflammation
macrophage
mouse
nonhuman
phagocytosis
phenotype
priority journal
protein expression
salivary gland
Sjoegren syndrome
submandibular gland
Acinar Cells
Animals
Apoptosis
Autoimmune Diseases
Cell Survival
Cells, Cultured
Cyclic AMP
Cyclic AMP-Dependent Protein Kinases
Disease Models, Animal
Macrophages
Mice
Mice, Inbred BALB C
Mice, Inbred NOD
NF-kappa B
Phagocytosis
Receptors, Vasoactive Intestinal Peptide
Sjogren's Syndrome
Submandibular Gland
Tumor Necrosis Factor-alpha
Vasoactive Intestinal Peptide
description Sjögren's syndrome (SS) is a chronic autoimmune disease characterized by a progressive oral and ocular dryness that correlates poorly with the autoimmune damage of the glands. It has been proposed that a loss of homeostatic equilibrium in the glands is partly responsible for salivary dysfunction with acinar cells involved actively in the pathogenesis of SS. The non-obese diabetic (NOD) mouse model of Sjögren's syndrome develops secretory dysfunction and early loss of glandular homeostatic mechanisms, with mild infiltration of the glands. Based on the vasodilator, prosecretory and trophic effects of the vasoactive intestinal peptide (VIP) on acini as well as its anti-inflammatory properties we hypothesized that the local expression of VIP/vasoactive intestinal peptide receptor (VPAC) system in salivary glands could have a role in acinar cell apoptosis and macrophage function thus influencing gland homeostasis. Here we show a progressive decline of VIP expression in submandibular glands of NOD mice with no changes in VPAC receptor expression compared with normal mice. The deep loss of endogenous VIP was associated with a loss of acinar cells through apoptotic mechanisms that could be induced further by tumour necrosis factor (TNF)-α and reversed by VIP through a cyclic adenosine-5'-monophosphate (cAMP)/protein kinase A (PKA)-mediated pathway. The clearance of apoptotic acinar cells by macrophages was impaired for NOD macrophages but a shift from inflammatory to regulatory phenotype was induced in macrophages during phagocytosis of apoptotic acinar cells. These results support that the decline in endogenous VIP/VPAC local levels might influence the survival/apoptosis intracellular set point in NOD acinar cells and their clearance, thus contributing to gland homeostasis loss. © 2011 The Authors. Clinical and Experimental Immunology © 2011 British Society for Immunology.
author Hauk, Vanesa Cintia
Calafat, Mario José
Larocca, Luciana
Fraccaroli, Laura Virginia
Grasso, Esteban Nicolás
Ramhorst, Rosanna Elizabeth
Pérez Leirós, Claudia
author_facet Hauk, Vanesa Cintia
Calafat, Mario José
Larocca, Luciana
Fraccaroli, Laura Virginia
Grasso, Esteban Nicolás
Ramhorst, Rosanna Elizabeth
Pérez Leirós, Claudia
author_sort Hauk, Vanesa Cintia
title Vasoactive intestinal peptide/vasoactive intestinal peptide receptor relative expression in salivary glands as one endogenous modulator of acinar cell apoptosis in a murine model of Sjögren's syndrome
title_short Vasoactive intestinal peptide/vasoactive intestinal peptide receptor relative expression in salivary glands as one endogenous modulator of acinar cell apoptosis in a murine model of Sjögren's syndrome
title_full Vasoactive intestinal peptide/vasoactive intestinal peptide receptor relative expression in salivary glands as one endogenous modulator of acinar cell apoptosis in a murine model of Sjögren's syndrome
title_fullStr Vasoactive intestinal peptide/vasoactive intestinal peptide receptor relative expression in salivary glands as one endogenous modulator of acinar cell apoptosis in a murine model of Sjögren's syndrome
title_full_unstemmed Vasoactive intestinal peptide/vasoactive intestinal peptide receptor relative expression in salivary glands as one endogenous modulator of acinar cell apoptosis in a murine model of Sjögren's syndrome
title_sort vasoactive intestinal peptide/vasoactive intestinal peptide receptor relative expression in salivary glands as one endogenous modulator of acinar cell apoptosis in a murine model of sjögren's syndrome
publishDate 2011
url https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00099104_v166_n3_p309_Hauk
http://hdl.handle.net/20.500.12110/paper_00099104_v166_n3_p309_Hauk
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