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

Abstract

Objectives:
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.
Methods:
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.
Results:
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.
Conclusions:
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

Conference

ConferenceIADR General session Washington
CountryUnited States
CityWashington
Period21/03/201324/03/2013

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