Yamakawa Kazuya, Matsuo Junji, Okubo Torahiko, Nakamura Shinji, Yamaguchi Hiroyuki
Department of Medical Laboratory Science, Faculty of Health Sciences, Hokkaido University, Sapporo, Hokkaido 060-0812, Japan.
Division of Biomedical Imaging Research, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan.
J Infect Chemother. 2018 Feb;24(2):130-137. doi: 10.1016/j.jiac.2017.10.007. Epub 2017 Nov 11.
Chlamydia trachomatis is the leading cause of sexually transmitted infections worldwide. Capsaicin, a component of chili pepper, which can stimulate actin remodeling via capsaicin receptor TRPV1 (transient receptor potential vanilloid 1) and anti-inflammatory effects via PPARγ (peroxisome proliferator-activated receptor-γ) and LXRα (liver X receptor α), is a potential candidate to control chlamydial growth in host cells. We examined whether capsaicin could inhibit C. trachomatis growth in immortal human epithelial HeLa cells. Inclusion forming unit and quantitative PCR assays showed that capsaicin significantly inhibited bacterial growth in cells in a dose-dependent manner, even in the presence of cycloheximide, a eukaryotic protein synthesis inhibitor. Confocal microscopic and transmission electron microscopic observations revealed an obvious decrease in bacterial numbers to inclusions bodies formed in the cells. Although capsaicin can stimulate the apoptosis of cells, no increase in cleaved PARP (poly (ADP-ribose) polymerase), an apoptotic indicator, was observed at a working concentration. All of the drugs tested (capsazepine, a TRPV1 antagonist; 5CPPSS-50, an LXRα inhibitor; and T0070907, a PPARγ inhibitor) had no effect on chlamydial inhibition in the presence of capsaicin. In addition, we also confirmed that capsaicin inhibited Chlamydia pneumoniae growth, indicating a phenomena not specific to C. trachomatis. Thus, we conclude that capsaicin can block chlamydial growth without the requirement of host cell protein synthesis, but by another, yet to be defined, mechanism.
沙眼衣原体是全球性传播感染的主要病因。辣椒素是辣椒的一种成分，它可通过辣椒素受体TRPV1（瞬时受体电位香草酸亚型1）刺激肌动蛋白重塑，并通过PPARγ（过氧化物酶体增殖物激活受体γ）和LXRα（肝脏X受体α）发挥抗炎作用，是控制宿主细胞中衣原体生长的潜在候选物。我们研究了辣椒素是否能抑制永生人类上皮细胞HeLa中沙眼衣原体的生长。包涵体形成单位和定量PCR分析表明，辣椒素即使在存在真核蛋白质合成抑制剂放线菌酮的情况下，也能以剂量依赖的方式显著抑制细胞内细菌的生长。共聚焦显微镜和透射电子显微镜观察显示，细胞内形成的包涵体中的细菌数量明显减少。虽然辣椒素可刺激细胞凋亡，但在工作浓度下未观察到凋亡指标——裂解的PARP（聚（ADP-核糖）聚合酶）增加。所测试的所有药物（TRPV1拮抗剂辣椒平、LXRα抑制剂5CPPSS-50和PPARγ抑制剂T0070907）在辣椒素存在的情况下对衣原体抑制均无作用。此外，我们还证实辣椒素可抑制肺炎衣原体的生长，表明这一现象并非沙眼衣原体所特有。因此，我们得出结论，辣椒素可阻断衣原体生长，无需宿主细胞蛋白质合成，但通过另一种尚未明确的机制。
