Hyperglucose Contributes to Periodontitis: Involvement of the NLRP3 Pathway by Engaging the Innate Immunity of Oral Gingival Epithelium
Hyperglucose Contributes to Periodontitis: Involvement of the NLRP3 Pathway by Engaging the Innate Immunity of Oral Gingival Epithelium
复制标题
高血糖导致牙周炎：NLRP3 通路通过参与口腔牙龈上皮的先天免疫而参与其中
DOI：
10.1902/jop.2014.140403
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发表时间：
2015-02-01
影响因子：
4.3
通讯作者：
Zhang, Jincai
中科院分区：
文献类型：
--
作者：
Huang, Xin;Yang, Xi;Zhang, Jincai
背景资料：NLRP 3炎性小体本质上是细胞内先天免疫传感器家族，其可以响应细菌攻击并启动早期宿主免疫应答。然而，NLRP 3通路在慢性牙周炎（CP）和2型糖尿病（T2 DM）患者牙龈组织中的表达及其可能的分子机制尚未完全阐明。方法：收集CP和/或T2 DM患者牙龈组织，采用免疫组化方法检测NLRP 3和白细胞介素（IL）-1 β的表达。为探讨其可能的分子机制，体外建立人牙龈上皮细胞（HGECs），并用脂多糖（LPS）和/或高糖进行攻击。高细胞外K+被用作NLRP 3的抑制剂。结果：与对照组相比，CP和/或T2 DM患者牙龈上皮中NLRP 3和IL-1 β表达均显著上调（P < 0.05）。LPS或高糖刺激HGECs后NLRP 3表达显著上调（P = 0.00）。与单独LPS或高糖相比，LPS和高糖同时刺激导致NLRP 3表达显著上调（P = 0.00）。结论：对于T2 DM合并CP患者，高血糖状态可能通过激活NLRP 3通路而加重牙龈组织的炎症状态，这种异常的宿主炎症反应可能促进牙龈组织的进一步破坏。
Background: The NLRP3 inflammasome is essentially a family of intracellular innate immune sensors that can respond to bacterial challenge and initiate early host immunity responses. However, the involvement and possible molecular mechanism of the NLRP3 pathway in the context of chronic periodontitis (CP) and diabetes mellitus have yet to be fully elucidated.Methods: Gingival tissues were collected from patients with CP and/or type 2 diabetes mellitus (T2DM), and the expression of NLRP3 and interleukin (IL)-1 beta was analyzed by immunohistochemistry. To explore the possible molecular mechanism, human gingival epithelial cells (HGECs) were established in vitro and challenged with lipopolysaccharide (LPS) and/or high glucose. High extracellular K+ was applied as an inhibitor of NLRP3. The NLRP3 pathway was analyzed by immunocytochemistry and quantitative polymerase chain reaction.Results: Compared with control individuals, NLRP3 and IL-1 beta were significantly upregulated in oral gingival epithelium of patients with CP and/or T2DM (P < 0.05). The expression of NLRP3 was significantly upregulated in HGECs when stimulated in vitro by LPS or high glucose (P = 0.00). The simultaneous stimulation of LPS and high glucose contributed to significant upregulation of NLRP3 expression versus LPS or high glucose alone (P = 0.00). Although expression of caspase 1 and IL-1 beta protein were increased in HGECs when stimulated by LPS, they were partially inhibited after the NLRP3 was successfully blocked.Conclusion: For patients with T2DM and CP, hyperglycemic status may exacerbate the inflammation state of gingival tissue by activating the NLRP3 pathway, and this abnormal host inflammatory response may contribute to further tissue breakdown.