Journal
JOURNAL OF ORAL PATHOLOGY & MEDICINE
Volume 42, Issue 1, Pages 66-72Publisher
WILEY-BLACKWELL
DOI: 10.1111/j.1600-0714.2012.01181.x
Keywords
innate immunity; interferon; sjogren's syndrome; xerostomia
Categories
Funding
- National Institutes of Health, USA [R21DE019883, R01AI079621, R01DK069769]
- Sjogren's Syndrome Foundation USA
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R01AI079621] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DENTAL &CRANIOFACIAL RESEARCH [R21DE019883] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R01DK069769, R01DK089182] Funding Source: NIH RePORTER
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Background: 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. Methods: 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. Results: 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. Conclusions: 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 Sjogrens syndrome, elevated levels of type I IFNs and IL-6 can directly affect glandular function.
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