title: Effects of aging in the expression of NOD-like receptors and inflammasome-related genes in oral mucosa.
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.
authors.affiliation: Center for Oral Health Research, College of Dentistry, University of Kentucky, Lexington, KY, USA.
authors.forename: J L
authors.initials: JL
authors.lastname: Ebersole
authors.affiliation: Center for Oral Health Research, College of Dentistry, University of Kentucky, Lexington, KY, USA.
authors.forename: S
authors.initials: S
authors.lastname: Kirakodu
authors.affiliation: Center for Oral Health Research, College of Dentistry, University of Kentucky, Lexington, KY, USA.
authors.forename: M J
authors.initials: MJ
authors.lastname: Novak
authors.affiliation: Center for Oral Health Research, College of Dentistry, University of Kentucky, Lexington, KY, USA.
authors.forename: C R
authors.initials: CR
authors.lastname: Exposto
authors.affiliation: Department of Statistics, College of Arts and Sciences, University of Kentucky, Lexington, KY, USA.
authors.forename: A J
authors.initials: AJ
authors.lastname: Stromberg
authors.affiliation: Department of Statistics, College of Arts and Sciences, University of Kentucky, Lexington, KY, USA.
authors.forename: S
authors.initials: S
authors.lastname: Shen
authors.affiliation: School of Dental Medicine, University of Puerto Rico, San Juan, Puerto Rico.
authors.forename: L
authors.initials: L
authors.lastname: Orraca
authors.affiliation: Caribbean Primate Research Center, University of Puerto Rico, Toa Baja, Puerto Rico.
authors.forename: J
authors.initials: J
authors.lastname: Gonzalez-Martinez
authors.affiliation: Center for Oral Health Research, College of Dentistry, University of Kentucky, Lexington, KY, USA.
authors.forename: O A
authors.initials: OA
authors.lastname: Gonzalez
mesh_terms: D000375:Aging / Q000235:genetics*; D000818:Animals; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D007113:Immunity, Innate / Q000235:genetics; D058847:Inflammasomes / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D053583:Interleukin-1beta / Q000096:biosynthesis; D008253:Macaca mulatta; D008297:Male; D009061:Mouth Mucosa / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D000070576:NLR Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D051616:Neuronal Apoptosis-Inhibitory Protein / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D010518:Periodontitis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction
chemical_list: D002352:Carrier Proteins; D058847:Inflammasomes; D053583:Interleukin-1beta; D000070576:NLR Proteins; D051616:Neuronal Apoptosis-Inhibitory Protein; D012333:RNA, Messenger
keywords: Aging; NOD-like receptors; inflammasome; innate immunity; oral mucosa