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Porphyromonas gingivalis RagB is a proinflammatory signal transducer and activator of transcription 4 agonist

J A Hutcherson1, J Bagaitkar, K Nagano

  • 1Department of Microbiology and Immunology, University of Louisville, Louisville, KY, USA.

Molecular Oral Microbiology
|November 25, 2014
PubMed

Insights

The RagB protein from Porphyromonas gingivalis significantly triggers inflammation in human monocytes by activating Toll-like receptors. This finding suggests RagB

Area of Science:

  • Oral microbiology
  • Immunology
  • Periodontal disease research

Background:

  • Periodontal diseases stem from chronic inflammation triggered by plaque.
  • Porphyromonas gingivalis is a key pathogen in periodontitis.
  • The RagB outer membrane protein's role in nutrient transport is known, but its interaction with the innate immune response is unexplored.

Purpose of the Study:

  • To investigate the role of the Porphyromonas gingivalis RagB protein in modulating the innate immune response.
  • To determine if RagB influences the expression of pro-inflammatory mediators in human monocytes.

Main Methods:

  • Exposure of primary human monocytes to purified RagB protein.
  • Analysis of gene expression for inflammatory mediators (e.g., IL-1α, IL-1β, IL-6, IL-8, CCL2).
  • Assessment of cytokine secretion (TNF, IL-8).
  • Investigation of RagB's interaction with Toll-like receptors (TLR2, TLR4) using blocking antibodies, inhibitors, and gene silencing.
  • Comparison with a ΔragB mutant.

Main Results:

  • RagB exposure induced dose-dependent expression of multiple pro-inflammatory genes in human monocytes.
  • RagB stimulated the secretion of tumor necrosis factor and IL-8.
  • RagB acted as a Toll-like receptor 2 and TLR4 agonist, activating STAT4 and NF-κB signaling pathways.
  • A RagB-deficient mutant showed reduced inflammatory capacity, which was restored upon complementation.

Conclusions:

  • RagB protein from Porphyromonas gingivalis elicits a significant pro-inflammatory response in human monocytes.
  • RagB's activation of TLR2 and TLR4 pathways contributes to periodontitis pathogenesis.
  • RagB may play a crucial role in the development of periodontitis and associated systemic complications.
Keywords:
Porphyromonas gingivalisToll-like receptorinflammationmonocyteperiodontitissignal transducer and activator of transcription 4

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