Dihydroceramides Derived from Bacteroidetes Species Sensitize TRPV1 Channels.

Bacterial colonization of open wounds is common, and patients with infected wounds often report significantly elevated pain sensitivity at the wound site. Transient Receptor Potential Vanilloid Type 1 (TRPV1) channels are known to play an important role in pain signaling and may be sensitized under pro-inflammatory conditions. Bacterial membrane components, such as phosphoethanolamine dihydroceramide (PEDHC), phosphoglycerol dihydroceramide (PGDHC), and lipopolysaccharide (LPS), are released in the environment from the Gram-negative bacteria of the Bacteroidetes species colonizing the infected wounds. Here, we used intracellular calcium imaging and patch-clamp electrophysiology approaches to determine whether bacterially derived PEDHC, PGDHC, or LPS can modulate the activity of the TRPV1 channels heterologously expressed in HEK cells. We found that PEDHC and PGDHC can sensitize TRPV1 in a concentration-dependent manner, whereas LPS treatment does not significantly affect TRPV1 activity in HEK cells. We propose that sensitization of TRPV1 channels by Bacteroidetes-derived dihydroceramides may at least in part underlie the increased pain sensitivity associated with wound infections.

开放性伤口的细菌定植很常见，伤口感染的患者经常报告伤口部位的疼痛敏感性显著升高。瞬时受体电位香草酸亚型1（TRPV1）通道已知在疼痛信号传导中起重要作用，并且在促炎条件下可能会被致敏。细菌膜成分，如磷酸乙醇胺二氢神经酰胺（PEDHC）、磷酸甘油二氢神经酰胺（PGDHC）和脂多糖（LPS），由定植在感染伤口的拟杆菌属革兰氏阴性菌释放到环境中。在此，我们使用细胞内钙成像和膜片钳电生理学方法来确定细菌衍生的PEDHC、PGDHC或LPS是否能够调节在人胚肾（HEK）细胞中异源表达的TRPV1通道的活性。我们发现PEDHC和PGDHC能够以浓度依赖的方式使TRPV1致敏，而LPS处理对HEK细胞中的TRPV1活性没有显著影响。我们提出，拟杆菌属衍生的二氢神经酰胺对TRPV1通道的致敏作用可能至少在一定程度上是与伤口感染相关的疼痛敏感性增加的原因。