An Interplay Between Gingival Fibroblasts and Monocytes - Implications in Periodontitis

Mark Lappin, Svetislav Zaric, C.E. Shelburne, Christopher Irwin, Wilson Coulter

Research output: Contribution to conferencePoster


Chronic periodontitis is characterised by a constant interaction of the microorganisms in subgingival dental plaque and host defence mechanisms resulting in exaggerated host immune and inflammatory response leading to tissue destruction. Endotoxin tolerance is a protective mechanism in which repeated exposure of host immune cells to lipopolysaccharide (LPS) results in repressed expression of pro-inflammatory cytokines and enhanced bacterial clearance. We examined induction of endotoxin tolerance in human gingival fibroblasts and THP-1 mononuclear cell line repeatedly exposed to two different isoforms of Porphyromonas gingivalis LPS.
THP-1 cells and human gingival fibroblasts were treated with P.gingivalis LPS isoforms 1435 and 1690 and IL-8 and TNF-α production was measured in the cells supernatants by ELISA after first and repeated challenge. In addition, IκB-α degradation was detected in the whole cell lysates. Canonical, E.coli LPS, was used as a positive control.
THP-1 cells treated with P.gingivalis LPS 1690 responded with a substantial production of both IL-8 and TNF-α. Repeated exposure to this type of LPS resulted in significantly decreased expression of TNF-α but sustained high production of IL-8. Human gingival fibroblasts treated with P.gingivalis LPS 1690 did not display endotoxin tolerance with regard to IL-8 synthesis but the level of TNF-α was undetectable. In contrast, P.gingivalis LPS 1435 did not trigger a significant increase in IL-8 production in either THP-1 cells or gingival fibroblasts and it was further inhibited by repeated exposure to this type of LPS. IL-8 secretion was IκB-α dependent while the production of TNF-α was inhibited by epigenetic silencing.
Our results indicate that impaired and partial endotoxin tolerance induced in mononuclear cells and gingival fibroblasts by P.gingivalis LPS 1690, characterised by augmented secretion of IL-8 and diminished production of TNF-α, could be responsible for detrimental consequences this bacterium exerts on periodontal tissues.
Original languageEnglish
Publication statusPublished - 22 Mar 2013
EventIADR General session Washington - Washington, United States
Duration: 21 Mar 201324 Mar 2013


ConferenceIADR General session Washington
CountryUnited States

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