Journal
MOLECULAR ORAL MICROBIOLOGY
Volume 28, Issue 3, Pages 204-218Publisher
WILEY
DOI: 10.1111/omi.12016
Keywords
chemokine response; chronic inflammation; inflammatory response; repeated bacterial challenge
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In periodontitis, tissue damage results mainly from aberrant host responses to oral microorganisms. Fibroblasts can play an important role in this. Gingival fibroblasts do not develop tolerance against the lipopolysaccharide of Porphyromonas gingivalis, a keystone pathogen in periodontitis, which may partly explain the persistence of inflammation. However, besides lipopolysaccharide, live P.gingivalis possess numerous virulence traits to impair host-responses. We hypothesized that fibroblast-responsiveness to a bacterial challenge could be affected by live P.gingivalis. We investigated if inflammatory responses of gingival fibroblasts to P.gingivalis were altered, when the fibroblasts had encountered P.gingivalis previously. On consecutive days, primary human gingival fibroblasts were challenged twice for 6h with live P.gingivalis, or fibroblasts were preincubated for 24h with a lower concentration of live P.gingivalis and re-challenged for 6h with a higher concentration. As the P.gingivalis capsule and proteases are involved in modulating host responses, we used encapsulated P.gingivalis W83 and a non-encapsulated mutant, and P.gingivalis ATCC33277 and a lys-gingipain and arg-gingipain mutant, to challenge fibroblasts. With all P.gingivalis-strains, interleukin-8 and monocyte chemoattractant protein-1 responses to the second challenge were less strong in fibroblasts that had been challenged with P.gingivalis before. These lower responses might correspond with higher interleukin-1 receptor agonist expression. Fibroblast responses to a second challenge were not influenced by 24h preincubation. Reduced chemokine responses after consecutive potent P.gingivalis challenges indicate that gingival fibroblast responsiveness is affected by a previous bacterial encounter. In periodontitis, such reduced chemokine responses may impair chemotaxis and clearance of oral microorganisms, thereby leading to prolonged inflammatory responses and tissue damage.
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