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

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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.