Radtke Christine, Sinis Nektarios, Sauter Michael, Jahn Sabrina, Kraushaar Udo, Guenther Elke, Rodemann H Peter, Rennekampff Hans-Oliver
Department of Plastic, Hand and Reconstructive Surgery, Burn Center, Hannover Medical School, Germany.
J Burn Care Res. 2011 Jan-Feb;32(1):150-9. doi: 10.1097/BCR.0b013e318203350c.
Cell death via necrosis and apoptosis is a hallmark of deep dermal to full-thickness cutaneous burn injuries. Keratinocytes might act as thermosensory cells that transmit information regarding ambient temperature via heat-gated transient receptor potential vanilloid (TRPV) ion channels. The aim of this study was to investigate the distribution of TRPV1, 2, 3, and 4 in uninjured and thermally burned skin. The authors investigated warmth-evoked currents in keratinocytes and cell kinetics of thermally injured keratinocytes in culture with agonists and antagonists of TRPV channels. Specimens of uninjured normal skin and discarded tissue of thermally injured skin were stained for TRPV1, 2, 3, and 4. Cultured primary human keratinocytes were heated for 5 minutes at the following temperatures: 37°C (control), 42°C, and 60°C and thereafter cultured for 24 or 48 hours at 37°C. Thermally stressed cells were treated with TRPV antagonists capsazepine or ruthenium red, and cell viability capacity was determined. TRPV1, TRPV2, TRPV3, and TRPV4 immunoreactivity was differentially identified on basal and suprabasal keratinocytes of healthy human skin. Patch clamp analysis showed a functional response of human keratinocytes at temperatures >40°C. Cell death of keratinocytes after heating at 42°C was reduced by 15 and 5% with ruthenium red and by 20 and 30% by capsazepine at 24 and 48 hours, respectively. Cell death after treatment at 60°C was significantly reduced at 24 hours with capsazepine (22%) or ruthenium red (18%) but only minimally affected after 48 hours postinjury. Interaction with TRPV channels on keratinocytes may offer a new strategy to counteract cell death after thermal injury.
通过坏死和凋亡导致的细胞死亡是深度真皮至全层皮肤烧伤的一个标志。角质形成细胞可能作为热感觉细胞，通过热门控瞬时受体电位香草酸（TRPV）离子通道传递有关环境温度的信息。本研究的目的是调查TRPV1、2、3和4在未受伤和热烧伤皮肤中的分布。作者用TRPV通道的激动剂和拮抗剂研究了角质形成细胞中温热诱发的电流以及培养的热损伤角质形成细胞的细胞动力学。对未受伤的正常皮肤标本和热损伤皮肤的废弃组织进行TRPV1、2、3和4染色。将培养的原代人角质形成细胞在以下温度下加热5分钟：37°C（对照）、42°C和60°C，然后在37°C下培养24或48小时。用TRPV拮抗剂辣椒素或钌红处理热应激细胞，并测定细胞活力。在健康人皮肤的基底和基底上层角质形成细胞上分别鉴定出TRPV1、TRPV2、TRPV3和TRPV4免疫反应性。膜片钳分析显示，人角质形成细胞在温度>40°C时有功能反应。在42°C加热后，角质形成细胞的细胞死亡在24小时和48小时时分别被钌红减少了15%和5%，被辣椒素减少了20%和30%。在60°C处理后，辣椒素（22%）或钌红（18%）在24小时时可显著减少细胞死亡，但在损伤后48小时影响最小。与角质形成细胞上的TRPV通道相互作用可能为对抗热损伤后细胞死亡提供一种新策略。
