Department of Oral and Maxillofacial Surgery, School of Dentistry, Pusan National University, Yangsan, Korea.
Department of Dental Anesthesia and Pain Medicine, School of Dentistry, Pusan National University, Dental Research Institute, Yangsan, Korea.
Int J Med Sci. 2020 Sep 9;17(16):2496-2504. doi: 10.7150/ijms.49909. eCollection 2020.
To maintain the normal pregnancy, suppression of inflammatory signaling pathway is a crucial physiologic response. Dexmedetomidine has been used for labor analgesia or supplement of inadequate regional analgesia during delivery. And it has been reported that dexmedetomidine has an anti-inflammatory effect. In this study, we examined the influence of dexmedetomidine on the expression of cyclooxygenase-2 (COX-2), prostaglandin E (PGE) and inflammatory cytokines in lipopolysaccharide (LPS)-stimulated human amnion-derived WISH cells. In addition, we evaluated the association of mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB) pathway in anti-inflammatory effect of dexmedetomidine. Human amnion-derived WISH cells were pretreated with various concentrations of dexmedetomidine (0.001-1 µg/ml) for 1 h and after then treated with LPS (1 µg/ml) for 24 h. MTT assay was conducted to evaluate the cytotoxicity. Nitric oxide (NO) production was analyzed using Griess-reaction microassay. RT-PCR was performed for analysis of mRNA expressions of COX-2, PGE, tumor necrosis factor (TNF)-α and interlukin (IL)-1β. Protein expressions of COX-2, PGE, p38 and NF-κB were analyzed by western blotting. LPS and dexmedetomidine had no cytotoxic effect on WISH cells. There was no difference in NO production after dexmedetomidine pretreatment. The mRNA and protein expressions of COX-2 and PGE were decreased by dexmedetomidine pretreatment in LPS-treated WISH cells. Dexmedetomidine also attenuated the LPS-induced mRNA expression of TNF-α and IL-1β. The activation of p38 and NF-κB was suppressed by dexmedetomidine pretreatment in LPS-treated WISH cells. We demonstrated that dexmedetomidine pretreatment suppressed the expressions of inflammatory mediators increased by LPS. In addition, this study suggests that anti-inflammatory effect of dexmedetomidine on WISH cells was mediated by the inhibitions of p38 and NF-κB activation.
为了维持正常妊娠，抑制炎症信号通路是一种至关重要的生理反应。右美托咪定已被用于分娩时的镇痛或补充不足的区域镇痛。并且已经报道右美托咪定具有抗炎作用。在这项研究中，我们研究了右美托咪定对脂多糖（LPS）刺激的人羊膜衍生 WISH 细胞中环氧化酶-2（COX-2）、前列腺素 E（PGE）和炎症细胞因子表达的影响。此外，我们评估了丝裂原活化蛋白激酶（MAPK）和核因子 kappa B（NF-κB）通路在右美托咪定抗炎作用中的相关性。
用人羊膜衍生的 WISH 细胞用不同浓度的右美托咪定（0.001-1μg/ml）预处理 1 小时，然后用 LPS（1μg/ml）处理 24 小时。MTT 法评估细胞毒性。用 Griess 反应微量分析法分析一氧化氮（NO）的产生。用 RT-PCR 分析 COX-2、PGE、肿瘤坏死因子（TNF）-α和白细胞介素（IL）-1β的 mRNA 表达。用 Western blot 分析 COX-2、PGE、p38 和 NF-κB 的蛋白表达。
LPS 和右美托咪定对 WISH 细胞没有细胞毒性作用。右美托咪定预处理后 NO 的产生没有差异。LPS 处理的 WISH 细胞中，右美托咪定预处理降低了 COX-2 和 PGE 的 mRNA 和蛋白表达。右美托咪定还减弱了 LPS 诱导的 TNF-α和 IL-1β的 mRNA 表达。LPS 处理的 WISH 细胞中，右美托咪定预处理抑制了 p38 和 NF-κB 的激活。
我们证明右美托咪定预处理抑制了 LPS 增加的炎症介质的表达。此外，这项研究表明，右美托咪定对 WISH 细胞的抗炎作用是通过抑制 p38 和 NF-κB 激活介导的。
