title: Local chemokine paralysis, a novel pathogenic mechanism for Porphyromonas gingivalis.
abstract: Periodontitis, which is widespread in the adult population, is a persistent bacterial infection associated with Porphyromonas gingivalis. Gingival epithelial cells are among the first cells encountered by both P. gingivalis and commensal oral bacteria. The chemokine interleukin 8 (IL-8), a potent chemoattractant and activator of polymorphonuclear leukocytes, was secreted by gingival epithelial cells in response to components of the normal oral flora. In contrast, P. gingivalis was found to strongly inhibit IL-8 accumulation from gingival epithelial cells. Inhibition was associated with a decrease in mRNA for IL-8. Antagonism of IL-8 accumulation did not occur in KB cells, an epithelial cell line that does not support high levels of intracellular invasion by P. gingivalis. Furthermore, a noninvasive mutant of P. gingivalis was unable to antagonize IL-8 accumulation. Invasion-dependent destruction of the gingival IL-8 chemokine gradient at sites of P. gingivalis colonization (local chemokine paralysis) will severely impair mucosal defense and represents a novel mechanism for bacterial colonization of host tissue.
authors.affiliation: Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle, Washington 98121, USA. rdarveau@u.washington.edu
authors.forename: R P
authors.initials: RP
authors.lastname: Darveau
authors.forename: C M
authors.initials: CM
authors.lastname: Belton
authors.forename: R A
authors.initials: RA
authors.lastname: Reife
authors.forename: R J
authors.initials: RJ
authors.lastname: Lamont
mesh_terms: D003773:Dental Plaque / Q000382:microbiology; D006801:Humans; D016209:Interleukin-8 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D007624:KB Cells; D010510:Periodontal Diseases / Q000209:etiology*; D016966:Porphyromonas gingivalis / Q000472:pathogenicity*; D012333:RNA, Messenger / Q000032:analysis
chemical_list: D016209:Interleukin-8; D012333:RNA, Messenger