LPS responsiveness in periodontal ligament cells is regulated by tumor necrosis factor-alpha.
Gingival fibroblasts function as accessory immune cells and are capable of synthesizing cytokines in response to lipopolysaccharides (LPS) from Gram-negative microbes. Recently, we have isolated, cloned, and characterized two cell lines which exhibit characteristics of periodontal ligament (PDL) cells. In this report, we demonstrate that PDL cells showing osteoblast-like phenotype are not LPS-responsive cells. However, treatment of PDL cells with tumor necrosis factor-alpha (TNF-alpha) inhibits the expression of their osteoblast-like characteristics. As a consequence of this TNF-alpha-induced phenotypic change, PDL cells become LPS-responsive, i.e., synthesize several pro-inflammatory cytokines in response to LPS. These phenotypic changes occur at concentrations of TNF-alpha that are frequently observed in tissue exudates during periodontal inflammation, suggesting a physiological significance for these in vitro observations. It is of interest that TNF-alpha-induced phenotypic changes in PDL cells are transient, since removal of rhTNF-alpha from the supernatants of PDL cell cultures results in re-acquisition of the osteoblast-like characteristics and lack of LPS responsiveness of PDL cells. These results suggest that TNF-alpha, by regulating the PDL cell functions, may allow these cells to participate in the disease process as accessory immune cells at the expense of their structural properties.
Division of Oral Biology, University of Pittsburgh, PA 15261, USA.
J C
JC
Quintero
N P
NP
Piesco
H H
HH
Langkamp
L
L
Bowen
S
S
Agarwal
D000469:Alkaline Phosphatase / Q000037:antagonists & inhibitors / Q000378:metabolism; D000938:Antigen-Presenting Cells / Q000276:immunology; D001483:Base Sequence; D002460:Cell Line; D017931:DNA Primers; D005347:Fibroblasts / Q000276:immunology; D006801:Humans; D007378:Interleukins / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008969:Molecular Sequence Data; D010006:Osteoblasts / Q000201:enzymology / Q000276:immunology; D015675:Osteocalcin / Q000096:biosynthesis; D010513:Periodontal Ligament / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology*; D010641:Phenotype; D012333:RNA, Messenger / Q000032:analysis; D011994:Recombinant Proteins / Q000494:pharmacology; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology / Q000502:physiology*
D017931:DNA Primers; D007378:Interleukins; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D015675:Osteocalcin; D000469:Alkaline Phosphatase