Huang Xin, Yang Xi, Ni Jia, Xie Baoyi, Liu Yeungyeung, Xuan Dongying, Zhang Jincai
Department of Periodontology, Guangdong Provincial Stomatological Hospital, Southern Medical University, Guangzhou, Guangdong, China.
J Periodontol. 2015 Feb;86(2):327-35. doi: 10.1902/jop.2014.140403. Epub 2014 Oct 17.
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.
Gingival tissues were collected from patients with CP and/or type 2 diabetes mellitus (T2DM), and the expression of NLRP3 and interleukin (IL)-1β 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.
Compared with control individuals, NLRP3 and IL-1β 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-1β protein were increased in HGECs when stimulated by LPS, they were partially inhibited after the NLRP3 was successfully blocked.
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.
NLRP3炎性小体本质上是一类细胞内天然免疫传感器家族，可对细菌攻击作出反应并启动早期宿主免疫反应。然而，NLRP3途径在慢性牙周炎（CP）和糖尿病背景下的参与情况及可能的分子机制尚未完全阐明。
收集CP和/或2型糖尿病（T2DM）患者的牙龈组织，通过免疫组织化学分析NLRP3和白细胞介素（IL）-1β的表达。为探究可能的分子机制，体外建立人牙龈上皮细胞（HGECs）并用脂多糖（LPS）和/或高糖进行刺激。应用高细胞外钾（K+）作为NLRP3的抑制剂。通过免疫细胞化学和定量聚合酶链反应分析NLRP3途径。
与对照组相比，CP和/或T2DM患者口腔牙龈上皮中NLRP3和IL-1β显著上调（P<0.05）。体外受LPS或高糖刺激时，HGECs中NLRP3的表达显著上调（P = 0.00）。与单独使用LPS或高糖相比，LPS和高糖同时刺激导致NLRP3表达显著上调（P = 0.00）。尽管LPS刺激时HGECs中半胱天冬酶1和IL-1β蛋白表达增加，但NLRP3成功阻断后它们受到部分抑制。
对于T2DM和CP患者，高血糖状态可能通过激活NLRP3途径加剧牙龈组织的炎症状态，这种异常的宿主炎症反应可能导致进一步的组织破坏。
