Targeted TNF-α Overexpression Drives Salivary Gland Inflammation

A. Limaye, B. E. Hall, L. Zhang, A. Cho, M. Prochazkova, C. Zheng, M. Walker, F. Adewusi, P. D. Burbelo, Z. J. Sun, I. S. Ambudkar, J. C. Dolan, B. L. Schmidt, A. B. Kulkarni

Research output: Contribution to journalArticle

Abstract

Chronic inflammation of the salivary glands from pathologic conditions such as Sjögren’s syndrome can result in glandular destruction and hyposalivation. To understand which molecular factors may play a role in clinical cases of salivary gland hypofunction, we developed an aquaporin 5 (AQP5) Cre mouse line to produce genetic recombination predominantly within the acinar cells of the glands. We then bred these mice with the TNF-αglo transgenic line to develop a mouse model with salivary gland–specific overexpression of TNF-α; which replicates conditions seen in sialadenitis, an inflammation of the salivary glands resulting from infection or autoimmune disorders such as Sjögren’s syndrome. The resulting AQP5-Cre/TNF-αglo mice display severe inflammation in the salivary glands with acinar cell atrophy, fibrosis, and dilation of the ducts. AQP5 expression was reduced in the salivary glands, while tight junction integrity appeared to be disrupted. The immune dysregulation in the salivary gland of these mice led to hyposalivation and masticatory dysfunction.

Original languageEnglish (US)
Pages (from-to)713-719
Number of pages7
JournalJournal of dental research
Volume98
Issue number6
DOIs
StatePublished - Jun 1 2019

Keywords

  • acinar cells
  • aquaporin 5
  • sialadenitis
  • tight junctions
  • transgenic mouse
  • xerostomia

ASJC Scopus subject areas

  • Dentistry(all)

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    Limaye, A., Hall, B. E., Zhang, L., Cho, A., Prochazkova, M., Zheng, C., Walker, M., Adewusi, F., Burbelo, P. D., Sun, Z. J., Ambudkar, I. S., Dolan, J. C., Schmidt, B. L., & Kulkarni, A. B. (2019). Targeted TNF-α Overexpression Drives Salivary Gland Inflammation. Journal of dental research, 98(6), 713-719. https://doi.org/10.1177/0022034519837240