Wang Xian, Chen Xin, Gao Jie, Jin Zuolin
State Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Clinical Research Center for Oral Diseases, Department of Orthodontics, School of Stomatology, The Fourth Military Medical University, No. 169 Changle West Road, Xi'an 710032, China.
Stem Cells Int. 2024 Dec 20;2024:7461604. doi: 10.1155/sci/7461604. eCollection 2024.
Transient receptor potential ankyrin 1 (TRPA1) molecule is an important type of transient receptor potential (TRP) cation channels, which can cause extracellular Ca to flow into cells after activation. TRPA1 plays an important role in acute and chronic pain, inflammation, kidney disease, cough and asthma, osteoarthritis, cardiovascular disease, obesity, diabetes, and other diseases. In this study, the expression of interleukin (IL)-1, IL-6, and IL-8 in periodontal ligament stem cells (PDLSCs) treated by lipopolysaccharide (LPS) and the effect of LPS on PDLSCS proliferation were detected. Meanwhile, the change in TRPA1 expression in PDLSCs treated by LPS was also assessed. By knocking down the expression of TRPA1 and using the TRPA1 antagonist HC-030031, the expression of IL-1, IL-6, and IL-8 in PDLSCs treated by LPS was downregulated. After LPS stimulation, the proliferation ability of PDLSCs decreased, the gene expression and secretion of IL-1, IL-6, and IL-8 increased and the gene and protein expression of TRPA1 were upregulated. Reducing the expression of TRPA1 can effectively inhibit the increase of gene expression of IL-1, IL-6, and IL-8 after LPS stimulation, and pretreatment of PDLSCs with HC-030031 can also achieve the above effect. And research has found that HC-030031 can inhibit the phosphorylation level of JNK in PDLSCs treated by LPS. The use of JNK inhibitor JNK-IN-8 can also reduce the expression of IL-1, IL-6, and IL-8 in PDLSCs. Finally, this study found LPS could cause the upregulation of TRPA1, and the inhibition of TRPA1 could produce an anti-inflammatory effect in PDLSCs treated by LPS due to its inhibition of JNK phosphorylation.
瞬时受体电位锚蛋白1（TRPA1）分子是瞬时受体电位（TRP）阳离子通道的一种重要类型，激活后可使细胞外钙离子流入细胞。TRPA1在急慢性疼痛、炎症、肾脏疾病、咳嗽和哮喘、骨关节炎、心血管疾病、肥胖、糖尿病等疾病中发挥重要作用。本研究检测了脂多糖（LPS）处理牙周膜干细胞（PDLSCs）后白细胞介素（IL）-1、IL-6和IL-8的表达以及LPS对PDLSCs增殖的影响。同时，还评估了LPS处理的PDLSCs中TRPA1表达的变化。通过敲低TRPA1的表达并使用TRPA1拮抗剂HC-030031，LPS处理的PDLSCs中IL-1、IL-6和IL-8的表达下调。LPS刺激后，PDLSCs的增殖能力下降，IL-1、IL-6和IL-8的基因表达和分泌增加，TRPA1的基因和蛋白表达上调。降低TRPA1的表达可有效抑制LPS刺激后IL-1、IL-6和IL-8基因表达的增加，用HC-030031预处理PDLSCs也可达到上述效果。并且研究发现HC-030031可抑制LPS处理的PDLSCs中JNK的磷酸化水平。使用JNK抑制剂JNK-IN-8也可降低PDLSCs中IL-1、IL-6和IL-8的表达。最后，本研究发现LPS可导致TRPA1上调，抑制TRPA1可在LPS处理的PDLSCs中产生抗炎作用，因为其抑制了JNK磷酸化。
