Substance P,keratinocytes,cathelicidin,NF-κB,rosacea ,"/> P物质通过激活NF-κB诱导人角质形成细胞产生抗菌肽

中国麻风皮肤病杂志 ›› 2023, Vol. 39 ›› Issue (6): 403-408.doi: 10.12144/zgmfskin202306403

• 论著 • 上一篇    下一篇

P物质通过激活NF-κB诱导人角质形成细胞产生抗菌肽

段萌,董炳琦,廖志锴,雷铁池   

  1. 武汉大学人民医院皮肤科，湖北武汉，430060
  • 出版日期:2023-06-15 发布日期:2023-05-18

Stimulation of cathelicidin in cultured human keratinocytes by Substance P via the activation of nuclear factor NF-κB

DUAN Meng, DONG Bingqi, LIAO Zhikai, LEI Tiechi   

  1. Department of Dermatology, Renmin Hospital of Wuhan University, Wuhan 430060, China
  • Online:2023-06-15 Published:2023-05-18

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摘要： 目的：明确P物质和FK-506对人角质形成细胞产生抗菌肽（CAMP）和NF-κB信号活化的影响。方法：P物质单独或联合FK-506处理培养HaCaT细胞24h，用实时荧光定量PCR检测CAMP mRNA表达，免疫蛋白印迹法检测CAMP蛋白表达，免疫荧光染色观察CAMP蛋白原位表达及NF-κB/p65核转位。结果：P物质刺激HaCaT细胞CAMP mRNA及蛋白表达增加，其中1 μM处理24 h效果最明显，与空白对照组比差异有统计学意义（P<0.05）；此外，P物质处理30 min可诱导HaCaT细胞NF-κB/p65发生核转位，此后随处理时间延长核转位减弱，与空白对照组比较差异有统计学意义（P<0.05）。FK-506抑制P物质诱导HaCaT细胞NF-κB/p65核转位并减低了P物质刺激的CAMP表达，P物质与FK-506联合处理组与P物质组比较，两组间差异具有统计学意义（P<0.05）。 结论：P物质通过激活NF-κB信号诱导角质形成细胞产生抗菌肽。针对抑制“P物质-NF-κB信号活化-抗菌肽”机制可能是治疗玫瑰痤疮的潜在新靶点。

关键词: P物质, 人角质形成细胞, CAMP, NF-κB, 玫瑰痤疮

Abstract: Objective: To explore the effects of Substance P (SP) and FK-506 on the production of cathelicidin CAMP and the activation of NF-κB in human keratinocytes. Methods: The HaCaT cells were cultured in vitro and treated with SP and/or FK-506 for 24 h. The expression levels of CAMP mRNA and protein were detected by qRT-PCR and western blotting respectively. The nuclear translocation of NF-κB/p65 was visualized by using an immunofluorescence staining. Results: The upregulations of CAMP mRNA and protein were detected in the cells treated with SP, of which the cells treated with 1μM SP for 24h showed the maximum stimulation effect, with a significant difference compared with untreated group (P<0.05). The nuclear translocation of NF-κB/p65 protein was also observed in HaCaT cells treated with SP for 30 min, with a significant difference compared with untreated cells (P<0.05). Thereafter, the nuclear translocation of NF-κB/p65 was diminished with time. FK-506 exerted a potent suppression in the nuclear translocation of NF-κB/p65 and in the expression of CAMP.  There was a statistically significant difference between the group treated with SP alone and the group treated in combination of SP and FK-506 (P<0.05). Conclusion: SP induces the production of cathelicdin in cultured keratinocytes through the activation of NF-κB signaling pathway. The regimens aiming at suppression of “SP-NF-κB activation-cathelicidin” might be a potential new target for the treatment of rosacea.

Key words: Substance P')">

Substance P, keratinocytes, cathelicidin, NF-κB, rosacea