fa Salivary gland hypofunction induced by activation of innate immunity is dependent on type I interferon signaling بیماری های دهان Oral Medicine پژوهشي Research <p> <strong>Background:</strong>  Activation of innate immunity through polyinosinic:polycytidylic acid [poly(I:C)] causes acute salivary gland hypofunction. As a major consequence of poly(I:C) treatment is type I interferon (IFN) production, this study was undertaken to investigate their role in salivary gland dysfunction. </p><p> <strong>Methods:</strong>  Different strains of mice deficient in either interferon alpha receptor (IFNAR1−/−) or IL-6−/−, or IL-10−/−, or EBI3−/− were treated with poly(I:C). Salivary gland function was determined by measuring pilocarpine-induced saliva volume. Gene expression levels were measured by real-time PCR. Ca2+ mobilization studies were performed using ex-vivo acinar cells. </p><p> <strong>Results:</strong>  A single injection of poly(I:C) rapidly induced salivary gland hypofunction in wild-type B6 mice (41% drop in saliva volumes compared to PBS-treated mice). In contrast, the loss of function in poly(I:C)-treated IFNAR−/− mice was only 9.6%. Gene expression analysis showed reduced levels of Il-6, Il-10, and Il-27 in submandibular glands of poly(I:C)-treated IFNAR−/− mice. While salivary gland dysfunction in poly(I:C)-treated IL-10−/− and EBI3−/− mice was comparable to wild-type mice, the IL-6−/− mice were more resistant, with only a 21% drop in function. Pilocarpine-induced Ca2+ flux was significantly suppressed in acinar cells obtained from poly(I:C)-treated wild-type mice. <strong>Conclusions:</strong>  Our data demonstrate that a combined action of type I IFNs and IL-6 contributes toward salivary gland hypofunction. This happens through interference with Ca2+ mobilization within acinar cells. Thus, in acute viral infections and diseases like Sjögren’s syndrome, elevated levels of type I IFNs and IL-6 can directly affect glandular function. </p><hr><p></p><p> <strong>Source: </strong>Journal of Oral Pathology & Medicine</p><p><a href="http://onlinelibrary.wiley.com/doi/10.1111/j.1600-0714.2012.01181.x/abstract" target="_blank"><font color="#0000ff"> Full Text</font></a></p> innate immunity;interferon;sjogren’s syndrome;xerostomia 0 0 http://idai.ir/browse.php?a_code=A-10-32-2218&slc_lang=fa&sid=1 Seshagiri-Rao Nandula 100319475328460010448 100319475328460010448 No Division of Nephrology, Center for Immunity Inflammation and Regenerative Medicine, University of Virginia, Charlottesville, VA, USA Paromita Dey 100319475328460010449 100319475328460010449 No Division of Nephrology, Center for Immunity Inflammation and Regenerative Medicine, University of Virginia, Charlottesville, VA, USA Kathryn L. Corbin 100319475328460010450 100319475328460010450 No Division of Endocrinology and Metabolism, University of Virginia, Charlottesville, VA, USA Craig S. Nunemaker 100319475328460010451 100319475328460010451 No Division of Endocrinology and Metabolism, University of Virginia, Charlottesville, VA, USA Harini Bagavant 100319475328460010452 100319475328460010452 No Division of Nephrology, Center for Immunity Inflammation and Regenerative Medicine, University of Virginia, Charlottesville, VA, USA/Department of Pharmacology, University of Virginia, Charlottesville, VA, USA Umesh S. Deshmukh usd7w@virginia.edu 100319475328460010453 100319475328460010453 Yes Division of Nephrology, Center for Immunity Inflammation and Regenerative Medicine, University of Virginia, Charlottesville, VA, USA/Department of Pharmacology, University of Virginia, Charlottesville, VA, USA