title: Differential Gene Expression Profiles Reflecting Macrophage Polarization in Aging and Periodontitis Gingival Tissues.
abstract: Recent evidence has determined a phenotypic and functional heterogeneity for macrophage populations. This plasticity of macrophage function has been related to specific properties of subsets (M1 and M2) of these cells in inflammation, adaptive immune responses and resolution of tissue destructive processes. This investigation hypothesized that targeted alterations in the distribution of macrophage phenotypes in aged individuals, and with periodontitis would be skewed towards M1 inflammatory macrophages in gingival tissues. The study used a non-human primate model to evaluate gene expression profiles as footprints of macrophage variation in healthy and periodontitis gingival tissues from animals 3-23 years of age and in periodontitis tissues in adult and aged animals. Significant increases in multiple genes reflecting overall increases in macrophage activities were observed in healthy aged tissues, and were significantly increased in periodontitis tissues from both adults and aged animals. Generally, gene expression patterns for M2 macrophages were similar in healthy young, adolescent and adult tissues. However, modest increases were noted in healthy aged tissues, similar to those seen in periodontitis tissues from both age groups. M1 macrophage gene transcription patterns increased significantly over the age range in healthy tissues, with multiple genes (e.g. CCL13, CCL19, CCR7 and TLR4) significantly increased in aged animals. Additionally, gene expression patterns for M1 macrophages were significantly increased in adult health versus periodontitis and aged healthy versus periodontitis. The findings supported a significant increase in macrophages with aging and in periodontitis. The primary increases in both healthy aged tissues and, particularly periodontitis tissues appeared in the M1 phenotype.
authors.affiliation: a Center for Oral Health Research, College of Dentistry, University of Kentucky , Lexington , KY , USA .
authors.forename: O A
authors.initials: OA
authors.lastname: Gonzalez
authors.affiliation: a 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: a 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: b Department of Statistics , College of Arts and Sciences, University of Kentucky , Lexington , KY , USA .
authors.forename: A
authors.initials: A
authors.lastname: Stromberg
authors.affiliation: c Department of Biostatistics , College of Public Health, University of Puerto Rico , San Juan , PR , USA .
authors.forename: R
authors.initials: R
authors.lastname: Nagarajan
authors.affiliation: a Center for Oral Health Research, College of Dentistry, University of Kentucky , Lexington , KY , USA .
authors.forename: C B
authors.initials: CB
authors.lastname: Huang
authors.affiliation: d Microarray Core Facility, College of Medicine, University of Puerto Rico , San Juan , PR , USA .
authors.forename: K C
authors.initials: KC
authors.lastname: Chen
authors.affiliation: e School of Dental Medicine, University of Puerto Rico , San Juan , PR , USA , and.
authors.forename: L
authors.initials: L
authors.lastname: Orraca
authors.affiliation: f Caribbean Primate Research Center, University of Puerto Rico , San Juan , PR , USA.
authors.forename: J
authors.initials: J
authors.lastname: Martinez-Gonzalez
authors.affiliation: a Center for Oral Health Research, College of Dentistry, University of Kentucky , Lexington , KY , USA .
authors.forename: J L
authors.initials: JL
authors.lastname: Ebersole
mesh_terms: D000367:Age Factors; D000375:Aging / Q000235:genetics* / Q000276:immunology; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D005881:Gingiva / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008253:Macaca mulatta; D008262:Macrophage Activation / Q000235:genetics / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism*; D008297:Male; D010518:Periodontitis / Q000235:genetics* / Q000276:immunology; D059467:Transcriptome
keywords: Aging; gene expression; gingival tissue; macrophage polarization; periodontitis