Salivary gland hypofunction induced by activation of innate immunity is dependent on type I interferon signaling

Seshagiri Rao Nandula, Paromita Dey, Kathryn L. Corbin, Craig S. Nunemaker, Harini Bagavant, Umesh S. Deshmukh

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

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 Sjögren's syndrome, elevated levels of type I IFNs and IL-6 can directly affect glandular function.

Original languageEnglish (US)
Pages (from-to)66-72
Number of pages7
JournalJournal of Oral Pathology and Medicine
Volume42
Issue number1
DOIs
StatePublished - Jan 2013

Keywords

  • Innate immunity
  • Interferon
  • Sjogren's syndrome
  • Xerostomia

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