Effects of biphenyl sulfonylamino methyl bisphosphonic acids on Porphyromonas gingivalis and cytokine secretion by oral epithelial cells.
Bisphosphonate drugs are well known to inhibit osteoclastic activity and have been proposed for the management of bone diseases, including periodontitis which is associated with alveolar bone destruction. In this study, we evaluated the effects of four arylsulfonamide bisphosphonates on growth of the periodontopathogenic bacterium Porphyromonas gingivalis as well as their capacity to reduce cytokine secretion by lipopolysaccharide (LPS)-stimulated oral epithelial cells. The growth of P. gingivalis was inhibited by (4'-Chloro-biphenyl-4-sulfonylamino)methyl-1,1- bisphosphonic acid while the three other arylsulfonamide bisphosphonates ((4-Methoxy-phenylsulfonylamino)methyl-1,1- bisphosphonic acid, (4-Nitro-phenylsulfonylamino)methyl-1,1-bisphosphonic acid, and (Biphenyl-4-sulfonylamino) methyl-1,1-bisphosphonic acid) had no effect. Growth inhibition was more pronounced under an iron-restricted condition. All four arylsulfonamide bisphosphonates decreased the production of the pro-inflammatory cytokines IL-6 and IL-8 by Aggregatibacter actinomycetemcomitans LPS-stimulated oral epithelial cells. In conclusion, we uncovered additional properties of bisphosphonates that may be beneficial for the treatment of periodontal diseases. In particular, (4'-Chlorobiphenyl- 4-sulfonylamino)methyl-1,1-bisphosphonic acid combines the already disclosed antiresoptive activity with antiinflammatory and antibacterial properties.
Department of Periodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, PR China.
Lei
L
Zhao
Annie
A
Marquis
Vu Dang
VD
La
Mariangela
M
Agamennone
Fulvio
F
Loiodice
Paolo
P
Tortorella
Daniel
D
Grenier
D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D004164:Diphosphonates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D009061:Mouth Mucosa / Q000187:drug effects* / Q000378:metabolism*; D016966:Porphyromonas gingivalis / Q000187:drug effects*; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D001713:Biphenyl Compounds; D016207:Cytokines; D004164:Diphosphonates; D013449:Sulfonamides