Vasoactive intestinal peptide inhibits tumor necrosis factor-alpha-induced apoptotic events in acinar cells from non-obese diabetic mice submandibular glands

IntroductionThe 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 non-obese diabetic (NOD) mouse model. Vasoactive intestinal peptide (VIP) has anti-inflammatory item in individual models of chronic inflammation. Our cause was to analyze the corollary of tumour necrosis factor-alpha (TNF-alpha) on apoptotic mediators in loney acinar cells from NOD submandibular gland and their modulation by VIP. Methods: Acinar cells were remoted from submandibular glands of 16 week aged NOD females with salivary flow decline. Age-matched BALB/c females or 8 week exhausted NOD females were used as controls. Apoptotic mediators and TNF-alpha receptor vocable were assessed by immunoblotting and RT-PCR, caspase 3 growth by optical density at 405 nm with Ac-DEVD-pNA as substrate and chromatin condensation by Hoechst. They were evaluated in resting conditions and after a 3.5 or 6 h culture with TNF-alpha. VIP part in acinar cells were assessed at 100 nM in TNF-alpha-treated cultures and VIP receptor functional assays by radio immunoassay (cAMP) or enzymatic detection (amylase). Results: NOD acinar cells at 16 weeks instruct an increased signal of TNF-alpha receptor1 calm with increased Bax, Tumor protein 53-induced nuclear protein 1 alpha (TP53INP1alpha), caspase 3 continuance and chromatin condensation. Acini from NOD mice were extra touchy to TNF-alpha-induced increase of apoptotic mediators than government cells. VIP inhibited TNF-alpha-induced apoptotic events through functional VPAC1 receptors coupled to protein kinase A (PKA) signaling pathway. Conclusions: Our results present that acinar cells isolated from submandibular glands of NOD mice with salivary dysfunction are more sensitive to apoptosis induced by TNF-alpha which could be prevented by VIP wound up a PKA-mediated pathway.

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