{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T18:34:46Z","timestamp":1773340486097,"version":"3.50.1"},"reference-count":40,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2009,4,8]],"date-time":"2009-04-08T00:00:00Z","timestamp":1239148800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"},{"start":{"date-parts":[[2009,4,8]],"date-time":"2009-04-08T00:00:00Z","timestamp":1239148800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Arthritis Res Ther"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                        <jats:title>Introduction<\/jats:title>\n                        <jats:p>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-\u03b1 on apoptotic mediators in isolated acinar cells from NOD submandibular gland and their modulation by VIP.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Methods<\/jats:title>\n                        <jats:p>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-\u03b1 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-\u03b1. VIP effects in acinar cells were assessed at 100 nM in TNF-\u03b1-treated cultures and VIP receptor functional assays by radio immunoassay (cAMP) or enzymatic detection (amylase).<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Results<\/jats:title>\n                        <jats:p>NOD acinar cells at 16 weeks present an increased expression of TNF-\u03b1 receptor1 together with increased Bax, tumour protein 53-induced nuclear protein1\u03b1 (TP53INP1\u03b1), caspase 3 activity and chromatin condensation. Acini from NOD mice were more sensitive to TNF-\u03b1-induced increases of apoptotic mediators than control cells. VIP inhibited TNF-\u03b1-induced apoptotic events through functional VPAC1 receptors coupled to the protein kinase A (PKA) signalling pathway.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Conclusions<\/jats:title>\n                        <jats:p>Our results indicate that acinar cells isolated from submandibular glands of NOD mice with salivary dysfunction are more sensitive to apoptosis induced by TNF-\u03b1 which could be prevented by VIP through a PKA-mediated pathway.<\/jats:p>\n                     <\/jats:sec>","DOI":"10.1186\/ar2671","type":"journal-article","created":{"date-parts":[[2009,4,8]],"date-time":"2009-04-08T18:13:52Z","timestamp":1239214432000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Vasoactive intestinal peptide inhibits TNF-\u03b1-induced apoptotic events in acinar cells from nonobese diabetic mice submandibular glands"],"prefix":"10.1186","volume":"11","author":[{"given":"Mario","family":"Calafat","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luciana","family":"Larocca","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valeria","family":"Roca","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vanesa","family":"Hauk","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicol\u00e1s","family":"Pregi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alcira","family":"Nesse","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudia","family":"P\u00e9rez Leir\u00f3s","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2009,4,8]]},"reference":[{"key":"2511_CR1","first-page":"1046","volume":"30","author":"V Strand","year":"1980","unstructured":"Strand V, Talal N: Advances in the diagnosis and concept of Sj\u00f6gren' syndrome (autoimmune exocrinopathy). 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