VIRALLY-INDUCED STAT-1, STAT-3 AND STAT-6

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。摘要：鼻窦息肉病影响了大约4%的普通人群。尽管积极的药物和手术治疗，复发率仍然高达60%。息肉产生的确切机制至今仍不清楚。息肉的组织学表现为水肿性液体间质周围增生的上皮，伴有密集的嗜酸性粒细胞浸润和稀疏的纤维细胞和粘液腺体。参与炎症和过度增生的炎性细胞因子在息肉中产生的水平增加。最近对哮喘患者的研究表明，呼吸道病毒感染是炎症级联反应的潜在刺激事件；细胞培养数据将上皮病毒感染与促炎细胞因子的表达增加联系起来。此外，哮喘和特应性上皮已被证明表达增加的表面ICAM-1（鼻病毒用于细胞进入的主要粘附分子）。信号转导和转录蛋白激活因子（STAT）是将细胞因子信号转化为基因表达的主要信号通路的一部分。病毒感染上皮的培养显示STAT-1和-3通路的激活。STAT-1产生特定的抗病毒反应，STAT-3对病原体产生更广泛的反应，而STAT-6被认为在过敏性炎症中起作用。STAT相关基因的转导导致促炎细胞因子的表达。本研究将验证stat信号通路在鼻息肉病发病机制中的活性。本研究将通过最常见的呼吸道病毒（流感病毒、副流感病毒、鼻病毒和呼吸道合胞病毒）的RT-PCR来阐明慢性病毒在息肉组织中的作用。STAT-1、STAT¿3和STAT-6水平将通过电泳迁移量转移法（EMSA）和免疫染色检测。基于我们将获得的数据，例如使用局部酪氨酸激酶抑制剂来抑制STAT激活，存在新的治疗方法的潜力。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Abstract: Sinonasal polyposis affects approximately 4% of the general population. Despite aggressive medical and surgical treatment, the recurrence rate remains as high as 60%. The exact mechanisms in polyp generation remain unclear to date. Polyp histology demonstrates hyperproliferative epithelium surrounding an edematous fluid stroma with dense eosinophilic infiltrate and sparse fibrous cells and mucous glands. Inflammatory cytokines involved in inflammation and hyperproliferation are produced at increased levels in polyps. Recent studies in asthmatics have established respiratory viral infection as a potential inciting event in the inflammatory cascade; cell culture data links viral infection of epithelium to increased expression of pro-inflammatory cytokines. Furthermore, asthmatic and atopic epithelium has been shown to express increased surface ICAM-1 (the primary adhesion molecule utilized by the Rhinovirus for cell entry). The signal transducers and activator of transcription proteins (STAT) are part of the major signaling pathway that convert cytokine signal into gene expression. Cultures of virus infected epithelium show activation of the STAT-1 and -3 pathways. STAT-1 produces a specific anti-viral response, STAT-3 produces a more generalized response to pathogens, and STAT-6 is thought to play a role in allergic inflammation. Transduction of STAT related genes results in expression of pro-inflammatory cytokines. This study will test the hypothesis that the STAT-signaling pathway is active in the pathogenesis of nasal polyposis. This study will elucidate the role of chronic viral presence in polyp tissue through RT-PCR of the most common respiratory viruses (influenza, parainfluenza, rhinovirus, and RSV). STAT-1, STAT¿3, and STAT-6 levels will be detected via electrophoretc mobility shift assay (EMSA), and via immunostaining. The potential for novel treatments exists based on the data we will obtain such as the use of topical tyrosine kinase inhibitors to inhibit STAT activation.