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.
Quintero
J C
JC
Division of Oral Biology, University of Pittsburgh, PA 15261, USA.
Piesco
N P
NP
Langkamp
H H
HH
Bowen
L
L
Agarwal
S
S
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