摘要
目的探讨Toll样受体7（TLR7）及其相关信号转导分子在人类乳头瘤病毒（HPV）感染和尖锐湿疣复发机制中的作用。方法用双色免疫荧光抗体染色流式细胞仪检测30例健康人、35例初发尖锐湿疣患者，32例复发尖锐湿疣患者和30例使用咪喹莫特联合氨基酮戊酸光动力疗法（ALA—PDT）治疗的复发性尖锐湿疣患者外周血不同亚群T细胞内TLR7的表达，使用SPSS13．0软件进行t检验。用Western印迹方法检测各组尖锐湿疣患者及健康人外周血CD3＋T细胞内接头蛋白MyD88及相关信号分子TRAF6、P13K、AKT、p42／44和核因子KB（NF—KB）等表达的变化。结果健康人外周血CD3＋CD4＋T细胞和CD3＋CD8＋T细胞内均可检测到TLR7的表达。与健康对照组比较，初发和复发尖锐湿疣患者外周血CD3＋CD8＋T细胞内TLR7的表达水平无显著改变，而CD3＋CD4＋T细胞内TLR7的表达明显增加（健康对照组为12．6％±6．3％，初发尖锐湿疣组为23．3％±8．4％，t=4．72，P〈0．01；复发尖锐湿疣组为32．8％±8．9％，t：10．76，P〈0．01）；与复发尖锐湿疣患者比较，咪喹莫特联合ALA—PDT治疗组尖锐湿疣患者外周血CD3＋CD4＋T细胞内TLR7的表达水平显著降低（20．3％±5．7％，t=5．41，P〈0．01）。初发和复发尖锐湿疣患者外周血CD3＋T细胞内MyD88、TRAF6、P13K、p42／44和NF—KB蛋白表达显著增加，而AKT蛋白表达变化不明显；咪喹莫特联合ALA—PDT治疗组尖锐湿疣患者外周血CD3＋T细胞内MyD88、TRAF6、p42／44和NF—KB蛋白表达显著降低。结论尖锐湿疣患者外周血CD3＋CD4＋T细胞内表达上调的TLR7可作为HPV病毒感染的识别受体，参与机体的抗HPV免疫应答。
Objective To explore the role of Toll-like receptor 7 （TLR7） and related signal transduction molecules in mechanisms underlying human papilloma virus （HPV） infection and condyloma acuminatum （CA） recurrence. Methods Peripheral blood was obtained from 30 healthy controls, 35 patients with primary CA, 32 patiens with recurrent CA and 30 patients with recurrent CA treated by imiquimod and ALA-PDT. Two-color flow cytometric analysis was used to detect TLR7 expression in different peripheral blood T cell subsets, Western blot to determine the expression levels of an adapter protein myeloid differentiation primary response gene 88 （MyD88）, and signaling molecules including tumor necrosis factor receptor-associated factor （TRAF6）, phosphatidylinositol3-kinase （PI3K）, protein kinase B （AKT）, p42/44 and nuclear factor-kappa B （NF-KB） in peripheral blood CD3＋ T cells, from these subjects. Statistical analysis was carried out by Student＇s t test using the software SPSS 13.0. Results TLR7 was expressed in peripheral blood CD3＋CD4＋ T cells and CD3＋CD8＋ T cells from the healthy controls. Compared with the healthy controls, the patients with primary and recurrent CA showed no significant changes in TLR7 expression in CD3＋CD8＋ T cells, but a statistical increase in TLR7 expression in CD3＋CD4＋ T cells （23.3% ＋ 8.4% and 32.8% ＋ 8.9% vs. 12.6% ＋ 6.3%, t = 4.72, 10.76, both P 〈 0.01）. Decreased expression of TLR7 in CD3＋CD4＋ T cells was observed in patients treated with imiquimod and ALA- PDT compared with the patients with recurrent CA （20.3% ±5.7% vs. 32.8% ＋8.9%, t = 5.41, P 〈 0.01）. The protein expressions of MyD88, TRAF6, PI3K, p42/44 and NF-KB were significantly increased in CD3＋ T cells,while the AKT protein expression experienced no significant changes in patients with primary or recurrent CA compared with the healthy controls. A significant decrease was observed in the protein expression of MyD88, TRAF6, p42/44 and NF-KB in the treated patients compared with those with recurrent CA. Conclusions TLRT, which is highly expressed in peripheral blood CD3＋CD4＋ T cells in patients with CA, may take part in the host immune response against HPV and serve as a recognition receptor for HPV infection.
出处
《中华皮肤科杂志》
CAS
CSCD
北大核心
2013年第5期332-335,共4页
Chinese Journal of Dermatology
基金
上海市卫生局科研课题（2010251）
