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Bacterial fimbriae activate human peripheral blood monocytes utilizing TLR2, CD14 and CD11a/CD18 as cellular
Tomohiko Ogawa1, Yasuyuki Asai, Masahito Hashimoto
1Department of Oral Microbiology, Asahi University School of Dentistry, Gifu, Japan. tomo527@dent.asahi-u.ac.jp
Abstract:
Bacterial fimbriae are associated with a specific adherence factor, adhesin, in their microbial etiology. Porphyromonas gingivalis, as an anaerobic Gram-negative periodontopathogenic organism, is known to possess fimbriae on its cell surfaces. In this study, we demonstrated that P. gingivalis fimbriae and an active synthetic peptide composed of residues 69 - 73 of thefimbrial subunit protein, ALTTE, induced IL-6 mRNA expression and cytokine production, p38 mitogen-activated protein (MAP) kinase phosphorylation, and NF-kappaB activation in human peripheral blood monocytes. P. gingivalis fimbriae and ALTTE also induced IL-6 production via human Toll-like receptor (TLR) 2, CD14, and CD11a/CD18 (LFA-1) molecules on human monocytes. These results suggest that P. gingivalis fimbriae and these degraded peptides may play an important role in the inflamed gingival and periodontal tissues seen in the development and progression of periodontal diseases.
Insights
Porphyromonas gingivalis fimbriae and a synthetic peptide fragment activate human monocytes, triggering inflammatory responses relevant to periodontal disease progression. This involves key signaling pathways and cell surface receptors.
Area of Science:
- Microbiology
- Immunology
- Periodontology
Background:
- Bacterial fimbriae, including those from Porphyromonas gingivalis, are crucial adherence factors in microbial pathogenesis.
- Porphyromonas gingivalis is an anaerobic Gram-negative bacterium implicated in periodontal diseases.
Purpose of the Study:
- To investigate the role of P. gingivalis fimbriae and a specific peptide (ALTTE) in activating human monocytes.
- To elucidate the molecular mechanisms underlying P. gingivalis-induced inflammation in monocytes.
Main Methods:
- Treatment of human peripheral blood monocytes with P. gingivalis fimbriae and the synthetic peptide ALTTE.
- Analysis of IL-6 mRNA expression, cytokine production, p38 MAP kinase phosphorylation, and NF-kappaB activation.
- Investigation of the involvement of Toll-like receptor 2 (TLR2), CD14, and CD11a/CD18 (LFA-1) in the cellular response.
Main Results:
- P. gingivalis fimbriae and ALTTE induced IL-6 mRNA expression and cytokine production in human monocytes.
- Both stimuli led to p38 MAP kinase phosphorylation and NF-kappaB activation.
- IL-6 production was mediated through TLR2, CD14, and CD11a/CD18 (LFA-1) on monocytes.
Conclusions:
- P. gingivalis fimbriae and the peptide ALTTE are potent activators of human monocytes, driving inflammatory responses.
- These findings highlight the potential role of P. gingivalis components in the pathogenesis of periodontal diseases.
- The study identifies specific molecular pathways and receptors involved in the inflammatory cascade initiated by P. gingivalis.