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Infection and Immunity, May 2007, p. 2540-2547, Vol. 75, No. 5
0019-9567/07/$08.00+0     doi:10.1128/IAI.01957-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Gingival Epithelial Cell Transcriptional Responses to Commensal and Opportunistic Oral Microbial Species{triangledown} ,{dagger}

Yoshiaki Hasegawa,1 Jeffrey J. Mans,1 Song Mao,1 M. Cecilia Lopez,2 Henry V. Baker,2 Martin Handfield,1* and Richard J. Lamont1

Department of Oral Biology and Center for Molecular Microbiology, College of Dentistry,1 Department of Molecular Genetics and Microbiology, College of Medicine, University of Florida, Gainesville, Florida2

Received 13 December 2006/ Returned for modification 28 January 2007/ Accepted 11 February 2007

Transcriptional profiling and ontology tools were utilized to define the biological pathways of gingival epithelial cells modulated by coculture with the oral commensal Streptococcus gordonii and the opportunistic commensal Fusobacterium nucleatum. Overall, F. nucleatum and S. gordonii perturbed the gingival epithelial cell transcriptome much less significantly than the oral pathogens Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans perturbed the transcriptome, indicating that there was a greater degree of host adaptation by the commensal species (M. Handfield, J. J. Mans, G. Zheng, M. C. Lopez, S. Mao, A. Progulske-Fox, G. Narasimhan, H. V. Baker, and R. J. Lamont, Cell. Microbiol. 7:811-823, 2005). The biological pathways significantly impacted by F. nucleatum and S. gordonii included the mitogen-activated protein kinase (MAPK) and Toll-like receptor signaling pathways. Differential regulation of GADD45 and DUSP4, key components of the MAPK pathway, was confirmed at the protein level by Western blotting. Modulation of the MAPK pathway is likely to affect host cell proliferation and differentiation. In addition, both the MAPK and Toll-like receptor pathways ultimately converge on cytokine gene expression. An enzyme-linked immunosorbent assay of secreted interleukin-6 (IL-6) and IL-8 demonstrated that F. nucleatum induced production of these cytokines, whereas S. gordonii inhibited secretion from the epithelial cells. Stimulation of secretion of proinflammatory cytokines from epithelial cells may reflect the invasive phenotype of F. nucleatum and contribute to the greater pathogenic potential of F. nucleatum than of S. gordonii.


* Corresponding author. Mailing address: Department of Oral Biology and Center for Molecular Microbiology, College of Dentistry, University of Florida, Gainesville, FL 32610-0424. Phone: (352) 846-0763. Fax: (352) 392-2361. E-mail: mhandfield{at}dental.ufl.edu

{triangledown} Published ahead of print on 16 February 2007.

{dagger} Supplemental material for this article may be found at http://iai.asm.org/.

Editor: J. B. Bliska


Infection and Immunity, May 2007, p. 2540-2547, Vol. 75, No. 5
0019-9567/07/$08.00+0     doi:10.1128/IAI.01957-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.




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