Antibiotic-induced Porphyromonas gingivalis LPS release and inhibition of LPS-stimulated cytokines by antimicrobial peptides.
Bacterial lipopolysaccharide (LPS) release during periodontal infection is a significant component of periodontal disease. We hypothesized that some bacterial LPS release results from bacterial exposure to antibiotics. Therefore, we examined the ability of various classes of antibiotics to induce LPS release from Porphyromonas gingivalis as well as the ability of antimicrobial peptides (AMPs) to inhibit purified LPS. All antibiotics tested against P. gingivalis were able to liberate 1.9-12.9 times more LPS as compared to untreated bacteria. Among the three AMPs tested, LL-37 was found to be the most potent inhibitor of cytokine (tumor necrosis factor-alpha, interleukin-1beta, interleukin-6) production and completely neutralized purified P. ginigivalis LPS activity in the chromogenic limulus amebocyte lysate (LAL) and whole blood cytokine stimulation assays. These observations suggest that therapeutic approaches utilizing AMPs as adjuncts to neutralize released LPS should be considered.
Walters
S M
SM
Immunology and Microbiology Branch, US Army Dental and Trauma Research Detachment, Walter Reed Army Institute of Research, Great Lakes Naval Training Center, Great Lakes, IL 60088, USA.
Dubey
V S
VS
Jeffrey
N R
NR
Dixon
D R
DR
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology*; D016866:Bacteroidaceae Infections / Q000188:drug therapy; D001773:Blood Cells / Q000187:drug effects / Q000378:metabolism; D054804:Cathelicidins / Q000494:pharmacology; D016207:Cytokines / Q000097:blood / Q000378:metabolism*; D054808:Histatins / Q000494:pharmacology; D006801:Humans; D008033:Limulus Test; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors* / Q000302:isolation & purification / Q000378:metabolism*; D009842:Oligopeptides / Q000494:pharmacology; D009994:Osmolar Concentration; D010518:Periodontitis / Q000188:drug therapy; D016966:Porphyromonas gingivalis / Q000187:drug effects* / Q000378:metabolism*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D013997:Time Factors
D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins; D016207:Cytokines; C068075:HTN3 protein, human; D054808:Histatins; D008070:Lipopolysaccharides; D009842:Oligopeptides; D011500:Protein Synthesis Inhibitors; C554541:lysyl-lysyl-valyl-valyl-phenylalanyl-tryptophyl-valyl-lysyl-phenylalanyl-lysine