VIP inhibits TNFá-induced apoptotic events in acinar cells from NOD submandibularr gland

CALAFAT M; LAROCCA L; ROCA V; HAUK V; AZZAM S; PEREZ LEIROS C

Buenos Aires

Congreso; III Iberoamerican Congress of Neuroimmunomodulation (NIM); 2009

Seccion Argentina de la ISNIM

The role of apoptotic secretory epithelium as a pro-inflammatory triggering- factor of exocrine dysfunction is currently explored in Sjögren’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 analyze the effect of TNF-α on apoptotic mediators in isolated acinar cells from NOD submandibular gland and their modulation by VIP. Acinar cells were isolated from submandibular glands of 16 week old NOD females. Apoptotic mediators and TNF-α receptor expression were assessed by immunoblotting and RT-PCR, caspase 3 activity and chromatin condensation by Hoechst. They were evaluated in resting conditions and after TNF-α. VIP effects in acinar cells were assessed in TNF-α–treated cultures and VIP receptor functional assays by RIA (cAMP) or enzymatic detection (amylase). NOD acinar cells were more sensitive to TNF-α-induced increase of apoptotic mediators than control cells. VIP inhibited TNF-α-induced apoptotic events through functional VPAC1 receptors coupled to PKA signaling pathway. The acinar cells isolated from submandibular glands of NOD mice are more sensitive to TNF-α-induced apoptosis which could be prevented by VIP through a PKA-mediated pathway.