Cruz Díaz Luis Antonio, Flores Miramontes María Guadalupe, Chávez Hurtado Paulina, Allen Kirk, Gonzalez Ávila Marisela, Prado Montes de Oca Ernesto
Molecular Biology Laboratory, Biosecurity Area, Pharmaceutical and Medical Biotechnology Unit (UBMF), Research Center in Technology and Design Assistance of Jalisco State (CIATEJ, AC), National Council of Science and Technology (CONACYT), Guadalajara, JAL, Mexico.
In silico Laboratory, UBMF, CIATEJ AC, CONACYT, Guadalajara, JAL, Mexico ; Lancaster Medical School, Lancaster University, Lancaster, UK.
Biomed Res Int. 2015;2015:714580. doi: 10.1155/2015/714580. Epub 2015 Mar 1.
Hosts' innate defense systems are upregulated by antimicrobial peptide elicitors (APEs). Our aim was to investigate the effects of hyperthermia, ultraviolet A rays (UVA), and ultraviolet C rays (UVC) as well as glucose and ascorbic acid (AA) on the regulation of human β-defensin 1 (DEFB1), cathelicidin (CAMP), and interferon-γ (IFNG) genes in normal human keratinocytes (NHK). The indirect in vitro antimicrobial activity against Staphylococcus aureus and Listeria monocytogenes of these potential APEs was tested. We found that AA is a more potent APE for DEFB1 than glucose in NHK. Glucose but not AA is an APE for CAMP. Mild hypo- (35°C) and hyperthermia (39°C) are not APEs in NHK. AA-dependent DEFB1 upregulation below 20 mM predicts in vitro antimicrobial activity as well as glucose- and AA-dependent CAMP and IFNG upregulation. UVC upregulates CAMP and DEFB1 genes but UVA only upregulates the DEFB1 gene. UVC is a previously unrecognized APE in human cells. Our results suggest that glucose upregulates CAMP in an IFN-γ-independent manner. AA is an elicitor of innate immunity that will challenge the current concept of late activation of adaptive immunity of this vitamin. These results could be useful in designing new potential drugs and devices to combat skin infections.
抗菌肽诱导剂(APE)可上调宿主的固有防御系统。我们的目的是研究热疗、紫外线A(UVA)和紫外线C(UVC)以及葡萄糖和抗坏血酸(AA)对正常人角质形成细胞(NHK)中人类β-防御素1(DEFB1)、组织蛋白酶(CAMP)和干扰素-γ(IFNG)基因调控的影响。测试了这些潜在APE对金黄色葡萄球菌和单核细胞增生李斯特菌的间接体外抗菌活性。我们发现,在NHK中,AA对DEFB1的诱导作用比葡萄糖更强。葡萄糖是CAMP的诱导剂,而AA不是。轻度低温(35°C)和热疗(39°C)在NHK中不是诱导剂。低于20 mM时,AA依赖的DEFB1上调可预测体外抗菌活性以及葡萄糖和AA依赖的CAMP和IFNG上调。UVC可上调CAMP和DEFB1基因,但UVA仅上调DEFB1基因。UVC是人类细胞中一种先前未被认识的诱导剂。我们的结果表明,葡萄糖以不依赖IFN-γ的方式上调CAMP。AA是一种固有免疫诱导剂,这将挑战目前关于这种维生素在适应性免疫后期激活的概念。这些结果可能有助于设计新的潜在药物和设备来对抗皮肤感染。