Dental infection of Porphyromonas gingivalis exacerbates high fat diet-induced steatohepatitis in mice
Dental infection of Porphyromonas gingivalis exacerbates high fat diet-induced steatohepatitis in mice
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DOI：
10.1007/s00535-012-0738-1
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发表时间：
2013-11-01
影响因子：
6.3
通讯作者：
Takata, Takashi
中科院分区：
文献类型：
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作者：
Furusho, Hisako;Miyauchi, Mutsumi;Takata, Takashi
我们研究了牙龈卟啉单胞菌（P.g.）的牙齿感染的影响，一种重要的牙周病原体，对NASH进展的影响，通过给小鼠喂食高脂肪饮食（HFD）并检查P.g. C57 BL/6 J小鼠喂食普通饮食（CD）或HFD 12周，然后每组中一半的小鼠感染P.g.从牙髓室（HFD-P.g. (-)、HFD-P.g.（+）、CD-P.g. (-)和CD-P.g. (+)).组织学和免疫组化检查，血清脂多糖（LPS）水平的测量和ELISA细胞因子在肝脏进行。然后，我们研究了来自P.g.（P.g.- LPS）对脂肪肝肝细胞的作用，并进行P.g.在NASH患者的肝活检样本中，LPS的血清水平在P.g.（+）团体。在HFD组中出现肝脏脂肪变性，并且在HFD-P. g中Mac 2阳性巨噬细胞的病灶突出。(+). P.G.在枯否细胞和肝细胞中检测到。有趣的是，仅在HFD-P.g.中观察到纤维化区域伴肝星状细胞增殖和胶原形成。(+).在脂肪变性肝细胞中，TLR 2的表达，P.g. LPS受体表达上调。P.g.-脂多糖进一步增加脂肪肝细胞中棕榈酸诱导的炎性小体和促炎细胞因子的mRNA水平。我们首次证明了P.G.存在于晚期纤维化的NASH患者的肝脏中。P.g.的牙齿感染可能通过上调P.g.- LPS-TLR 2通路和炎性小体的活化。因此，预防和/或消除P.g.通过牙科治疗感染可能对NASH的管理有有益的影响。
We investigated the effects of dental infection with Porphyromonas gingivalis (P.g.), an important periodontal pathogen, on NASH progression, by feeding mice a high fat diet (HFD)and examining P.g. infection in the liver of NASH patients.C57BL/6J mice were fed either chow-diet (CD) or HFD for 12 weeks, and then half of the mice in each group were infected with P.g. from the pulp chamber (HFD-P.g.(-), HFD-P.g.(+), CD-P.g.(-) and CD-P.g.(+)). Histological and immunohistochemical examinations, measurement of serum lipopolysaccharide (LPS) levels and ELISA for cytokines in the liver were performed. We then studied the effects of LPS from P.g. (P.g.-LPS) on palmitate-induced steatotic hepatocytes in vitro, and performed immunohistochemical detection of P.g. in liver biopsy specimens of NASH patients.Serum levels of LPS are upregulated in P.g.(+) groups. Steatosis of the liver developed in HFD groups, and foci of Mac2-positive macrophages were prominent in HFD-P.g.(+). P.g. was detected in Kupffer cells and hepatocytes. Interestingly, areas of fibrosis with proliferation of hepatic stellate cells and collagen formation were only observed in HFD-P.g.(+). In steatotic hepatocytes, expression of TLR2, one of the P.g.-LPS receptors, was upregulated. P.g.-LPS further increased mRNA levels of palmitate-induced inflammasome and proinflammatory cytokines in steatotic hepatocytes. We demonstrated for the first time that P.g. existed in the liver of NASH patients with advanced fibrosis.Dental infection of P.g. may play an important role in NASH progression through upregulation of the P.g.-LPS-TLR2 pathway and activation of inflammasomes. Therefore, preventing and/or eliminating P.g. infection by dental therapy may have a beneficial impact on management of NASH.