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Treponema denticola peptidoglycan induces the production of inflammatory mediators and matrix metalloproteinase 9 in macrophage‐like cells
Author(s) -
Tanabe SI.,
Bodet C.,
Grenier D.
Publication year - 2009
Publication title -
journal of periodontal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.31
H-Index - 83
eISSN - 1600-0765
pISSN - 0022-3484
DOI - 10.1111/j.1600-0765.2008.01141.x
Subject(s) - treponema denticola , peptidoglycan , biology , secretion , microbiology and biotechnology , macrophage , biochemistry , enzyme , in vitro , genetics , porphyromonas gingivalis , bacteria
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 α, interleukin‐1β 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.