Trans-cinnamic aldehyde inhibits Aggregatibacter actinomycetemcomitans-induced inflammation in THP-1-derived macrophages via autophagy activation
Trans-cinnamic aldehyde inhibits Aggregatibacter actinomycetemcomitans-induced inflammation in THP-1-derived macrophages via autophagy activation
复制标题
DOI：
10.1002/jper.17-0727
复制
发表时间：
2018-10-01
影响因子：
4.3
通讯作者：
Na, Hee Sam
中科院分区：
文献类型：
--
作者：
Chung, Jin;Kim, Sumi;Na, Hee Sam
背景：炎症是机体抵抗细菌感染的一种重要防御机制，可导致组织损伤。伴放线菌聚集杆菌（Aggregatibacteractinomycetemcomitans，Aa）是侵袭性牙周炎的主要致病菌，其特征是牙周牙周组织迅速破坏。反式肉桂醛是肉桂提取物中的一种重要生物活性成分，具有抗炎、抗氧化、解热、抗菌、抗癌等作用。本研究的目的是探讨反式肉桂醛对Aa感染人THP-1衍生的巨噬细胞和对Aa诱导的小鼠牙周炎的抗炎作用。方法：THP-1细胞分化与佛波酯12-肉豆蔻酸酯13-乙酸酯和活的Aa感染。在细菌感染前30分钟预处理反式肉桂醛。酶联免疫吸附试验（ELISA）检测细胞因子的产生，Western blot检测蛋白表达。Cyto-ID检测自噬体形成。进行活细胞计数以确定细菌粘附、内化和细胞内存活。实验性牙周炎引起的AAa口服小鼠，和微型计算机断层扫描被用来评估骨loss.Results：预处理的反式肉桂醛显着抑制AA刺激释放的肿瘤坏死因子-α和白细胞介素（IL）-1 β。反式肉桂醛预处理抑制AA诱导的TLR信号通路的表达以及JNK、p38和核因子（NF）-κ B B的磷酸化。此外，反式肉桂醛处理下调了pro-IL-1 β，caspase-1和炎性小体成分的表达。反式肉桂醛处理显著降低Aa的细胞内存活。此外，自噬体形成和自噬标记物包括Beclin-1、ATG 5和LC 3的表达增加。最后，trans-cinnamic aldehyde显着抑制骨丢失在AA诱导的小鼠periodontitis.Conclusions：Trans-cinnamic aldehyde抑制AA刺激的炎症反应的表达和抑制细胞内细菌的生存通过自噬激活。这些结果表明，反式肉桂醛可能作为一种抗炎剂的侵袭性牙周炎。
Background: Inflammation is an essential response against bacterial infection as a host defense mechanism, which can lead to tissue damage. Aggregatibacter actinomycetemcomitans (Aa) is major pathogen for aggressive periodontitis characterized by rapid destruction of periodontal tissue surrounding teeth. Trans-cinnamic aldehyde is a key bioactive compound of the cinnamon extracts, which has anti-inflammatory, antioxidant, antipyretic, antimicrobial, and anti-cancer properties. The objective of the present study was to investigate the anti-inflammatory effect of trans-cinnamic aldehyde against Aa infection in human THP-1 derived macrophages and on Aa-induced periodontitis in mice.Methods: THP-1 cells were differentiated with phorbol 12-mystristate 13-acetate and were infected with live Aa. Trans-cinnamic aldehyde was pretreated 30 minutes before the bacterial infection. Cytokine production was determined by enzyme-linked immunosorbent assay (ELISA) and protein expressions were detected by Western blot analysis. Autophagosome formation was detected by Cyto-ID. Viable cell count was carried out to determine bacterial adhesion, internalization, and intracellular survival. Experimental periodontitis was induced by inoculating Aa orally to mice, and micro-computed tomography was used to evaluate bone loss.Results: Pretreatment of trans-cinnamic aldehyde significantly inhibited Aa-stimulated release of tumor necrosis factor-alpha and interleukin (IL)-1 beta. Pretreatment of trans-cinnamic aldehyde inhibited Aa-induced expression of TLR signaling pathway as well as the phosphorylation of JNK, p38, and nuclear factor (NF)-kappa B. Also, trans-cinnamic aldehyde treatment downregulated the expression of pro-IL-1 beta, caspase-1, and inflammasome components. Trans-cinnamic aldehyde treatment significantly decreased intracellular survival of Aa. Moreover, the autophagosome formation and the expressions of autophagy markers including Beclin-1, ATG5, and LC3 were increased. Finally, trans-cinnamic aldehyde significantly inhibited bone loss in Aa-induced mouse periodontitis.Conclusions: Trans-cinnamic aldehyde inhibited Aa-stimulated expression of inflammatory responses and inhibited intracellular bacterial survival via autophagy activation. These results suggest that trans-cinnamic aldehyde may serve as an anti-inflammatory agent for aggressive periodontitis.