Masuzaki, H., Yamamoto, H., Kenyon, C.J., Elmquist, J.K., Morton, N.M., Paterson, J.M., Shinyama, H., Sharp, M.G., Fleming, S., Mullins, J.J., Seckl, J.R. and Flier, J.S. (2003) Transgenic Amplification of Glucocorticoid Action in Adipose Tissue Causes High Blood Pressure in Mice. The Journal of Clinical Investigation, 112, 83-90.
ABSTRACT: It has been proposed that 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), which activates glucocorticoids, plays a role in chronic inflammatory diseases including metabolic diseases, rheumatoid arthritis, and ulcerative colitis. We have recently reported that the expression of 11β-HSD1 is increased in the gingiva of patients with chronic periodontitis and in that of rats with ligature-induced periodontitis. In this study, to further demonstrate the involvement of 11β-HSD1 in chronic periodontitis, the expression of 11β-HSD1 was investigated in another rat model of experimental periodontitis induced by intragingival injection of lipopolysaccharide from Porphyromonas gingivalis (LPS-PG). Alveolar bone loss was observed two weeks after intragingival injection of LPS-PG. The level of 11β-HSD1 mRNA assessed by real-time reverse transcriptase-polymerase chain reaction was significantly elevated in LPS-PG-induced periodontitis compared with controls. The expression of 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2), which inactivates glucocorticoids, was not significantly different between control and LPS-PG-induced periodontitis. The expression of 11β-HSD1 was significantly correlated with that of TNF in LPS-PG-induced periodontitis. The increased expression of 11β-HSD1 protein in LPS-PG-induced periodontitis was confirmed by immunohistochemistry using anti-11β-HSD1 antibody. These results further suggest a role for 11β-HSD1 in the pathogenesis of chronic periodontitis.