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Treponema denticola peptidoglycan induces the production of inflammatory mediators and matrix metalloproteinase 9 in macrophage-like cells.

Abstract：

BACKGROUND AND OBJECTIVE:Treponema denticola is a key pathogen associated with periodontitis, a chronic inflammatory disease affecting tooth-supporting tissues. In the present study, we investigated the response of human macrophage-like cells to stimulation by peptidoglycan isolated from T. denticola. We also studied the effect of the peptidoglycan preparation on the phosphorylation state of kinases. MATERIAL AND METHODS:Monoblastic leukemia cells (U937 strain) were differentiated into adherent macrophage-like cells using phorbol myristic acid prior to being stimulated for 6 or 24 h with various amounts of T. denticola peptidoglycan. Secreted inflammatory mediators were quantified by enzyme-linked immunosorbent assays. The phosphorylation state of kinases was determined by immunoblotting. RESULTS:The T. denticola peptidoglycan preparation, which was non-toxic for macrophage-like U937 leukemia cells at the concentration used, significantly increased, in a dose-dependent manner, the secretion of the pro-inflammatory cytokines tumor necrosis factor alpha, interleukin-1beta and interleukin-6. It also increased the secretion of two potent chemokines, interleukin-8 (IL-8) and regulated on activation normal T cell expressed and secreted (RANTES). T. denticola peptidoglycan also induced a significant increase in the secretion of prostaglandin E(2) and matrix metalloproteinase 9 by macrophage-like cells. The phosphorylation state of several kinases, including extracellular regulated protein-serine kinase 2 (+99%), G protein-coupled receptor-serine kinase 2 (+50%), Yes-related protein-tyrosine kinase (+44%) and extracellular regulated protein-serine kinase 1 (+30%) also increased following stimulation with the peptidoglycan preparation. CONCLUSION:T. denticola peptidoglycan activates intracellular signaling pathways, leading to an increased production of inflammatory mediators by macrophage-like cells.

journal_name

J Periodontal Res

journal_title

Journal of periodontal research

authors

Tanabe SI,Bodet C,Grenier D

doi

10.1111/j.1600-0765.2008.01141.x

subject

Has Abstract

pub_date

2009-08-01 00:00:00

pages

503-10

issue

eissn

0022-3484

issn

1600-0765

pii

JRE1141

journal_volume

pub_type

杂志文章

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Treponema denticola peptidoglycan induces the production of inflammatory mediators and matrix metalloproteinase 9 in macrophage-like cells.