AIM2炎症小体调控IL-1β在HPV阳性上呼吸道乳头瘤的机制研究

随着HPV感染率增加，成人上呼吸道乳头状瘤的发病率逐年递增。治疗后仍有5-10%复发，且部分患者易恶变。我们前期研究发现HPV16阳性乳头状瘤中，IL-1α、IL-1R、IL-1β、AIM2和Caspase-1表达均增高；且IL-1β表达升高组较IL-1β降低组的复发及恶变风险升高。目前HPV是否通过AIM2/Caspase通路调控IL-1β表达，以及IL-1β促进HPV阳性乳头状瘤恶性转化的机制还不甚清楚。故通过构建不同HPV感染状态和目的基因敲除的细胞系及小鼠，从体内外实验探究HPV调控IL-1β表达升高的机制；利用已构建的基因敲除小鼠模型，从体内实验探究IL-1β调控乳头状瘤恶性转化的免疫相关机制；通过检测成人乳头状瘤患者的相关免疫因子的表达水平，验证上述指标的敏感性。该项目的实施有助于了解HPV阳性乳头状瘤的发生及恶变机制，为成人乳头状瘤患者提供早期筛查及预后的分子标志物。

With the increase of HPV infection rate, the incidence of adult upper respiratory tract papilloma increases year by year. After treatment, there are still 5-10% relapses, and some patients are prone to malignant transformation. Our previous study found that in HPV16-positive papilloma, the expression of IL-1α, IL-1R, IL-1β, AIM2 and Caspase-1 were all increased; and the group with increased IL-1β expression relapsed and malignant than the group with reduced IL-1β The risk is increased. It is not clear whether HPV regulates the expression of IL-1β through the AIM2 / Caspase pathway, and the mechanism by which IL-1β promotes the malignant transformation of HPV-positive papilloma.Therefore, by constructing cell lines and mice with different HPV infection states and target gene knockouts, the mechanism by which HPV regulates IL-1β expression increase is explored from in vivo and in vitro experiments; the established gene knockout mouse model is used to explore from in vivo experiments IL-1β regulates the immune-related mechanism of malignant transformation of papilloma; by detecting the expression levels of relevant immune factors in adult patients with papilloma, the sensitivity of the above indicators is verified. The implementation of this project helps to understand the occurrence and malignant mechanism of HPV-positive papilloma, and provides molecular markers for early screening and prognosis for adult patients with papilloma.