Departmental Papers (Dental)
Document Type
Journal Article
Date of this Version
11-12-2013
Publication Source
PLoS ONE
Volume
8
Issue
11
Start Page
e78541
DOI
10.1371/journal.pone.0078541
Abstract
P. gingivalis is a prominent periodontal pathogen that has potent effects on host cells. In this study we challenged gingival epithelial cells with P. gingivalis with the aim of assessing how mRNA levels of key target genes were modulated by P. gingivalis via the transcription factors FOXO1 and FOXO3. Primary mono- and multi-layer cultures of gingival epithelial cells were challenged and barrier function was examined by fluorescent dextran and apoptosis was measured by cytoplasmic histone associated DNA. Gene expression levels were measured by real-time PCR with and without FOXO1 and FOXO3 siRNA compared to scrambled siRNA. P. gingivalis induced a loss of barrier function and stimulated gingival epithelial cell apoptosis in multilayer cultures that was in part gingipain dependent. P. gingivalis stimulated an increase in FOXO1 and FOXO3 mRNA, enhanced mRNA levels of genes associated with differentiated keratinocyte function (keratin-1, -10, -14, and involucrin), increased mRNA levels of apoptotic genes (BID and TRADD), reduced mRNA levels of genes that regulate inflammation (TLR-2 and -4) and reduced those associated with barrier function (integrin beta-1, -3 and -6). The ability of P. gingivalis to modulate these genes was predominantly FOXO1 and FOXO3 dependent. The results indicate that P. gingivalis has pronounced effects on gingival keratinocytes and modulates mRNA levels of genes that affect host response, differentiation, apoptosis and barrier function. Moreover, this modulation is dependent upon the transcription factors FOXO1 or FOXO3. In addition, a new function for FOXO1 was identified, that of suppressing TLR-2 and TLR-4 and maintaining integrin beta -1, beta -3 and beta -6 basal mRNA levels in keratinocytes.
Copyright/Permission Statement
© 2013 Li et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Keywords
Apoptosis, Forkhead Transcription Factors, Gingiva, Humans, Keratinocytes, Porphyromonas gingivalis, RNA, Messenger
Recommended Citation
Li, S., Dong, G., Moschidis, A., Ortiz, J., Benakanakere, M. R., Kinane, D. F., & Graves, D. T. (2013). P. gingivalis Modulates Keratinocytes Through FOXO Transcription Factors. PLoS ONE, 8 (11), e78541-. http://dx.doi.org/10.1371/journal.pone.0078541
Included in
Bacterial Infections and Mycoses Commons, Medical Cell Biology Commons, Medical Genetics Commons, Oral Biology and Oral Pathology Commons
Date Posted: 02 April 2015
This document has been peer reviewed.