Effects of aging in the expression of NOD-like receptors and inflammasome-related genes in oral mucosa

J. L. Ebersole, S. Kirakodu, M. J. Novak, C. R. Exposto, A. J. Stromberg, S. Shen, L. Orraca, J. Gonzalez-Martinez, O. A. Gonzalez

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

Abstract

The molecular changes underlying the higher risk of chronic inflammatory disorders during aging remain incompletely understood. Molecular variations in the innate immune response related to recognition and interaction with microbes at mucosal surfaces could be involved in aging-related inflammation. We developed an ontology analysis of 20 nucleotide-binding and oligomerization domain (NOD)-like receptors (NLRs) and seven inflammasome-related genes (IRGs) in healthy and inflamed/periodontitis oral mucosal tissues from young, adolescent, adult, and aged non-human primates (Macaca mulatta) using the GeneChip® Rhesus Macaque Genome array. Validation of some of the significant changes was done by quantitative reverse transcription-polymerase chain reaction. The expression of NLRB/NAIP, NLRP12, and AIM2 increased with aging in healthy mucosa whereas NLRC2/NOD2 expression decreased. Although higher expression levels of some NLRs were generally observed with periodontitis in adult mucosal tissues (e.g. NLRB/NAIP, NLRP5, and NLRX1), various receptors (e.g. NLRC2/NOD2 and NLRP2) and the inflammasome adaptor protein ASC, exhibited a significant reduction in expression in aged periodontitis tissues. Accordingly, the expression of NLR-activated innate immune genes, such as HBD3 and IFNB1, was impaired in aged but not adult periodontitis tissues. Both adult and aged tissues showed significant increase in interleukin-1β expression. These findings suggest that the expression of a subset of NLRs appears to change with aging in healthy oral mucosa, and that aging-related oral mucosal inflammation could involve an impaired regulation of the inflammatory and antimicrobial response associated with downregulation of specific NLRs and IRGs.

Original languageEnglish
Pages (from-to)18-32
Number of pages15
JournalMolecular Oral Microbiology
Volume31
Issue number1
DOIs
StatePublished - Feb 1 2016

Bibliographical note

Funding Information:
This work was supported by National Institute of Health (NIH) grants P20GM103538 and UL1TR000117. We express our gratitude to the Caribbean Primate Research Center (CPRC) supported by grant P40RR03640 and the Microarray Core of University Kentucky for their invaluable technical assistance. Dr. Stromberg was also funded by NIH grant 5P20GM103436-13.

Publisher Copyright:
© 2016 John Wiley & Sons A/S.

Keywords

  • Aging
  • Inflammasome
  • Innate immunity
  • NOD-like receptors
  • Oral mucosa

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Dentistry (all)
  • Microbiology (medical)

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