Anti-inflammatory role of glucose-dependent insulinotropic polypeptide in periodontitis

葡萄糖依赖性胰岛素促泌多肽在牙周炎中的抗炎作用

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作者:Yuki Suzuki, Nobuhisa Nakamura, Megumi Miyabe, Toru Nishikawa, Shin-Ichi Miyajima, Kei Adachi, Makoto Mizutani, Takeshi Kikuchi, Ken Miyazawa, Shigemi Goto, Katsushi Tsukiyama, Yuichiro Yamada, Norikazu Ohno, Toshihide Noguchi, Akio Mitani, Tatsuaki Matsubara, Keiko Naruse

Conclusions

These results suggest the beneficial effects of GIP on periodontal disease. In diabetic patients, GIP is expected to have a direct anti-inflammatory effect on periodontitis in addition to its glucose-lowering effect.

Methods

Experimental periodontitis was induced by ligature wire in GIPRKO and C57BL/C mice. Two weeks after the ligature, immunohistological evaluation and inflammatory messenger ribonucleic acid expression in the gingiva was examined. To elucidate the role of GIP in inflammation, the effects of GIP on lipopolysaccharide-induced gene expressions in THP-1 cells were evaluated.

Results

Periodontitis increased inflammatory cell infiltration, macrophage accumulation and tumor necrosis factor-α and nitric oxide synthase gene expressions in the gingiva. Periodontitis in GIPRKO showed a marked increase of inflammatory cells in the gingivomucosal tissue. Mac-1-positive macrophages and the inflammatory gene expressions were significantly increased in periodontitis in GIPRKO compared with C57BL/C mice periodontitis. Immunohistochemical staining confirmed that GIP receptors were expressed in residual and infiltrated Mac-1-positive macrophages. The in vitro study showed that GIP suppressed lipopolysaccharide-induced tumor necrosis factor-α and nitric oxide synthase gene expression in a dose-dependent manner. Furthermore, the inhibitory effect of GIP on lipopolysaccharide-induced inflammatory gene expressions was at least partially through cyclic adenosine monophosphate/protein kinase A pathway. Conclusions: These results suggest the beneficial effects of GIP on periodontal disease. In diabetic patients, GIP is expected to have a direct anti-inflammatory effect on periodontitis in addition to its glucose-lowering effect.

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