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

Autor: Mario Jose Calafat, Rosanna Ramhorst, Luciana Larocca, E. Grasso, L. Fraccaroli, Vanesa Hauk, C. Pérez Leirós
Jazyk: angličtina
Rok vydání: 2011
Předmět:
Translational Studies
Receptor expression
Vasoactive intestinal peptide
Apoptosis
Nod
animal cell
Acinar Cells
Mice
Mice
Inbred NOD
homeostasis
Cyclic AMP
Immunology and Allergy
Receptor
Cells
Cultured
NOD mice
Mice
Inbred BALB C
tumor necrosis factor alpha
Vasoactive intestinal peptide receptor
article
NF-kappa B
phagocytosis
acinar cell
female
Sjogren's Syndrome
priority journal
submandibular gland
Tumor necrosis factor alpha
Sjögren's syndrome
vasoactive intestinal polypeptide
Acinar cell apoptosis and clearance
Vasoactive Intestinal Peptide
medicine.medical_specialty
phenotype
Cell Survival
Immunology
Submandibular Gland
animal experiment
salivary gland
macrophage
Biology
animal tissue
Autoimmune Diseases
cell isolation
stomatognathic system
Phagocytosis
Internal medicine
medicine
Acinar cell
Animals
controlled study
protein expression
mouse
cyclic AMP dependent protein kinase
nonhuman
Tumor Necrosis Factor-alpha
animal model
Macrophages
Cyclic AMP-Dependent Protein Kinases
VIP
Disease Models
Animal
Endocrinology
inflammation
Receptors
Vasoactive Intestinal Peptide
cell function
vasoactive intestinal polypeptide receptor 1
Sjoegren syndrome
Zdroj: Clin. Exp. Immunol. 2011;166(3):309-316
Biblioteca Digital (UBA-FCEN)
Universidad Nacional de Buenos Aires. Facultad de Ciencias Exactas y Naturales
instacron:UBA-FCEN
Popis: 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.
Databáze: OpenAIRE
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