Self-heat shock protein 60 induces tumour necrosis factor-alpha in monocyte-derived macrophage: possible role in chronic inflammatory periodontal disease.
Heat shock protein 60 (hsp60) has been increasingly recognized as an important molecule in infectious and autoimmune diseases. We have demonstrated previously that serum antibodies to both human hsp60 and Porphyromonas gingivalis GroEL were elevated in periodontitis patients compared with healthy subjects. In order to clarify the relative importance of hsp60 in the inflammatory response in periodontal disease, the stimulatory effect of human and bacterial hsp60 on the production of tumour necrosis factor-alpha (TNF-alpha) was examined in phorbol myristate acetate (PMA)-stimulated THP-1 cells. As bacterial hsp60s, recombinant P. gingivalis and Actinobacillus actinomycetemcomitans GroEL was used. Human hsp60 but not P. gingivalis or A. actinomycetemcomitans GroEL demonstrated stimulatory activity similar to lipopolysaccharide (LPS) derived from the bacteria. The activity of hsp60 was inhibited by anti-CD14 and anti-Toll-like receptor 4 (TLR4) antibodies, suggesting that both CD14 and TLR4 mediate hsp60 signalling. Immunohistochemical analysis demonstrated that hsp60 is abundantly expressed in periodontitis lesions. Therefore, it is postulated that periodontopathic bacteria stimulate the cells in the periodontium to up-regulate the expression of hsp60, which in turn may stimulate macrophage and possibly other cells to produce proinflammatory cytokines. These mechanisms may be involved in the chronicity and tissue destruction of periodontal disease.
Ueki
K
K
Division of Periodontology, Department of Oral Biological Sciences, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
Tabeta
K
K
Yoshie
H
H
Yamazaki
K
K
D002273:Carcinogens / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D018834:Chaperonin 60 / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D002908:Chronic Disease; D006801:Humans; D008262:Macrophage Activation / Q000276:immunology; D008264:Macrophages / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D009000:Monocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D010510:Periodontal Diseases / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000276:immunology
D002273:Carcinogens; D018834:Chaperonin 60; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D013755:Tetradecanoylphorbol Acetate