Vasoactive intestinal peptide inhibits TNF-α-induced apoptotic events in acinar cells from nonobese diabetic mice submandibular glands

Introduction: The role of apoptotic secretory epithelium as a pro-inflammatory triggering factor of exocrine dysfunction is currently explored in Sjogren's syndrome patients and in the nonobese diabetic (NOD) mouse model. Vasoactive intestinal peptide (VIP) has anti-inflammatory effects in vari...

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Detalles Bibliográficos
Autores principales: Calafat, M., Larocca, L., Roca, V., Hauk, V., Pregi, N., Nesse, A., Pérez Leirós, C.
Formato: JOUR
Materias:
amylase
caspase 3
cyclic AMP dependent protein kinase
nuclear protein
protein Bax
tumor necrosis factor alpha
tumor necrosis factor alpha receptor
tumor protein 53 induced nuclear protein 1 alpha
unclassified drug
vasoactive intestinal polypeptide
vasoactive intestinal polypeptide receptor 1
acinar cell
animal cell
animal experiment
animal model
animal tissue
apoptosis
article
controlled study
enzyme activity
enzyme substrate
female
mouse
nonhuman
nonobese diabetic mouse
protein expression
protein function
protein protein interaction
salivary gland disease
salivation
submandibular gland
animal
Bagg albino mouse
disease model
metabolism
pathology
physiology
reverse transcription polymerase chain reaction
signal transduction
Sjoegren syndrome
Western blotting
Animals
Apoptosis
Blotting, Western
Cyclic AMP-Dependent Protein Kinases
Disease Models, Animal
Female
Mice
Mice, Inbred BALB C
Mice, Inbred NOD
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction
Sjogren's Syndrome
Submandibular Gland
Tumor Necrosis Factor-alpha
Vasoactive Intestinal Peptide
Acceso en línea:http://hdl.handle.net/20.500.12110/paper_14786354_v11_n2_p_Calafat
Aporte de:
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires
Descripción
Sumario:Introduction: The role of apoptotic secretory epithelium as a pro-inflammatory triggering factor of exocrine dysfunction is currently explored in Sjogren's syndrome patients and in the nonobese diabetic (NOD) mouse model. Vasoactive intestinal peptide (VIP) has anti-inflammatory effects in various models of chronic inflammation. Our goal was to analyse the effect of TNF-α on apoptotic mediators in isolated acinar cells from NOD submandibular gland and their modulation by VIP. Methods: Acinar cells were isolated from submandibular glands of 16-week-old NOD females with salivary flow decline. Age-matched BALB/c females or eight-week-old NOD females were used as controls. Apoptotic mediators and TNF-α receptor expression were assessed by immunoblotting and RT-PCR, caspase 3 activity was assessed by optical density at 405 nm with Ac-DEVD-pNA as a substrate and chromatin condensation by Hoechst stain. They were evaluated in resting conditions and after a 3.5 or 6 hours of culture with TNF-α. VIP effects in acinar cells were assessed at 100 nM in TNF-α-treated cultures and VIP receptor functional assays by radio immunoassay (cAMP) or enzymatic detection (amylase). Results: NOD acinar cells at 16 weeks present an increased expression of TNF-α receptor1 together with increased Bax, tumour protein 53-induced nuclear protein1α (TP53INP1α), caspase 3 activity and chromatin condensation. Acini from NOD mice were more sensitive to TNF-α-induced increases of apoptotic mediators than control cells. VIP inhibited TNF-α-induced apoptotic events through functional VPAC1 receptors coupled to the protein kinase A (PKA) signalling pathway. Conclusions: Our results indicate that acinar cells isolated from submandibular glands of NOD mice with salivary dysfunction are more sensitive to apoptosis induced by TNF-α which could be prevented by VIP through a PKA-mediated pathway. © 2009 Calafat et al.; licensee BioMed Central Ltd.

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