Human papillomavirus-associated induction of human β-defensins in anal intraepithelial neoplasia
Human papillomavirus-associated induction of human β-defensins in anal intraepithelial neoplasia
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DOI：
10.1111/j.1365-2133.2009.09090.x
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发表时间：
2009-06-01
影响因子：
10.3
通讯作者：
Wieland, U.
中科院分区：
文献类型：
--
作者：
Kreuter, A.;Skrygan, M.;Wieland, U.
背景抗菌肽和抗菌蛋白（Antimicrobial peptides and proteins，AMPs）是广泛分布的天然免疫效应分子，具有抗菌活性。然而，关于AMP的抗病毒作用的信息很少。目的本研究分析了人类免疫缺陷病毒（HIV）阳性男性同性恋（MSM）的人乳头瘤病毒（HPV）相关肛门皮肤病变中AMP的表达，MSM是持续性HPV感染和肛门发育不良的特殊高危人群。RNA酶7和人β-防御素（hBD）-1，hBD-2和hBD-3。结果45例HIV阳性MSM伴肛门上皮内瘤变（AIN）、肛门尖锐湿疣或肛门黏膜正常者，8例HIV阴性MSM伴肛门尖锐湿疣者，皮损组织中均检测到AMP的表达，其中11例HPV阳性，16例HPV阳性，18例HPV阴性，31例HPV阳性，33例HPV阴性。分析AMP mRNA表达。另外，在总共45个样品中进行hBD-2和hBD-3的免疫组织化学分析。hBD-2和hBD-3基因和蛋白表达在AIN和尖锐湿疣中均显著增加，而LL-37、RNase 7和hBD-1基因表达与未受影响的肛门粘膜无显著差异。AMP的表达既不与HPV类型的数量相关，也不与量化类型的高危和低危HPV DNA载量相关。结论hBD-2和hBD-3在HIV阳性和HIV阴性MSM的HPV相关性肛门皮肤病变中的表达均显著上调。它们在天然免疫中对这些病变的生物学意义需要进一步研究。
Background Antimicrobial peptides and proteins (AMPs) are widely distributed effector molecules of the innate immune system with well-known antibacterial activity. However, there is a paucity of information regarding antiviral effects of AMPs.Objectives The present study was performed to analyse expression of AMPs in human papillomavirus (HPV)-associated anal skin lesions of human immunodeficiency virus (HIV)-positive men who have sex with men (MSM), a special high-risk group for persistent HPV infections and anal dysplasia.Methods Skin lesions were analysed for the presence of LL-37, RNase 7, and human beta-defensin (hBD)-1, hBD-2 and hBD-3. Moreover, HPV typing and HPV DNA load determination for HPV types 6, 11, 16, 18, 31 and 33 were performed to evaluate possible correlations between expression of AMPs and lesional HPV types.Results Skin biopsies of 45 HIV-positive MSM with anal intraepithelial neoplasia (AIN), anal condylomata acuminata or unaffected anal mucosa, as well as condylomata acuminata of eight HIV-negative MSM, were analysed for AMP mRNA expression. Additionally, immunohistochemical analysis for hBD-2 and hBD-3 was performed in a total of 45 samples. hBD-2 and hBD-3 gene and protein expression was significantly increased in both AIN and condyloma, whereas LL-37, RNase 7 and hBD-1 gene expression did not differ significantly from unaffected anal mucosa. AMP expression correlated neither with the number of HPV types nor with the high-risk and low-risk HPV DNA loads of the quantified types. No significant differences in AMP expression were observed in condylomata of HIV-positive and HIV-negative MSM.Conclusions hBD-2 and hBD-3 expression was shown to be significantly upregulated in HPV-associated anal skin lesions of both HIV-positive and HIV-negative MSM. Their biological significance in the innate immunity against these lesions needs further research.