Streptococcus cristatus attenuates Fusobacterium nucleatum-induced cytokine expression by influencing pathways converging on nuclear factor-κB

G. Zhang, J. D. Rudney

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

We previously reported that Streptococcus cristatus, an oral commensal, was able to downregulate the interleukin-8 (IL-8) response to Fusobacterium nucleatum, a putative oral pathogen in oral epithelial cells. The aim of this study was to extend the understanding of how S. cristatus regulates cytokine expression in oral epithelial cells on a broad basis, and investigate whether the modulation of a Toll-like receptor (TLR) pathway was involved in this process. KB and TERT-2 cells were co-cultured with F. nucleatum and S. cristatus, either alone or in combination. Total RNA was extracted and pathway-specific focused microarrays were used to profile the transcriptional responses of various cytokine genes and those related to TLR-mediated signal transduction. Reverse transcription-polymerase chain reactions (RT-PCR) and protein assays were performed to confirm the microarray results for selected genes. We found that exposure to either S. cristatus or F. nucleatum alone led to distinct changes in cytokine expression patterns. Fusobacterium nucleatum induced a greater number of gene expression changes than S. cristatus (15% vs. 4%, respectively). The presence of S. cristatus with F. nucleatum attenuated the expression of a number of inflammatory cytokines, and upregulated several anti-inflammatory mediators. The RT-PCR confirmed the messenger RNA attenuation of IL-1α, tumor necrosis factor-α and IL-6 by S. cristatus. Profiling of TLR-signaling-related genes revealed that S. cristatus most significantly impacted the downstream pathways, especially nuclear factor-κB, rather than altering TLRs and their adaptors and interacting proteins. Our data suggest that S. cristatus may attenuate the epithelial proinflammatory cytokine response to F. nucleatum by influencing pathways converging on nuclear factor-κB.

Original languageEnglish (US)
Pages (from-to)150-163
Number of pages14
JournalMolecular Oral Microbiology
Volume26
Issue number2
DOIs
StatePublished - Apr 2011

Keywords

  • Cytokines
  • Epithelial cells
  • Fusobacterium nucleatum
  • Inflammatory response
  • Nuclear factor-κB
  • Streptococcus cristatus

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