Lipoxin A4 Analogues Inhibit Leukocyte Recruitment to Porphyromonas gingivalis:  A Role for Cyclooxygenase-2 and Lipoxins in Periodontal Disease

M Pouliot, CB Clish, NA Petasis, TE Van Dyke… - Biochemistry, 2000 - ACS Publications
Biochemistry, 2000ACS Publications
The potential involvement of the inducible cyclooxygenase isoform (COX-2) and the role of
novel lipid mediators were investigated in the pathogenesis of periodontal disease.
Crevicular fluids from localized juvenile periodontitis (LJP) patients contained prostaglandin
(PG) E2 and 5-lipoxygenase-derived products, leukotriene B4, and the biosynthesis
interaction product, lipoxin (LX) A4. Neutrophils from peripheral blood of LJP patients, but
not from asymptomatic donors, also generated LXA4, suggesting a role for this …
The potential involvement of the inducible cyclooxygenase isoform (COX-2) and the role of novel lipid mediators were investigated in the pathogenesis of periodontal disease. Crevicular fluids from localized juvenile periodontitis (LJP) patients contained prostaglandin (PG)E2 and 5-lipoxygenase-derived products, leukotriene B4, and the biosynthesis interaction product, lipoxin (LX)A4. Neutrophils from peripheral blood of LJP patients, but not from asymptomatic donors, also generated LXA4, suggesting a role for this immunomodulatory molecule in periodontal disease. To characterize host responses of interest to periodontal pathogens, Porphyromonas gingivalis was introduced within murine dorsal air pouches. In the air pouch cavity, P. gingivalis elicited leukocyte infiltration, concomitant with elevated PGE2 levels in the cellular exudates, and upregulated COX-2 expression in infiltrated leukocytes. In addition, human neutrophils exposed to P. gingivalis also upregulated COX-2 expression. Blood borne P. gingivalis gave significant increases in the murine tissue levels of COX-2 mRNA associated with both heart and lungs, supporting a potential role for this oral pathogen in the evolution of systemic events. The administration of metabolically stable analogues of LX and of aspirin-triggered LX potently blocked neutrophil traffic into the dorsal pouch cavity and lowered PGE2 levels within exudates. Together, these results identify PMN as an additional and potentially important source of PGE2 in periodontal tissues. Moreover, they provide evidence for a novel protective role for LX in periodontitis, limiting further PMN recruitment and PMN-mediated tissue injury that can lead to loss of inflammatory barriers that prevent systemic tissue invasion of oral microbial pathogens.
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