The effect of rhinovirus infection on the expression of programmed cell death ligand and inflammatory cytokines in patients of allergic rhinitis

학위논문 (석사)-- 서울대학교 대학원 : 의학과, 2015. 8. 이재서.Background and Objectives: Rhinovirus (RV) is a common viral pathogen associated with upper respiratory infection (URI). There are complex interactions between allergic reaction and viral infection. Some studies suggest that patients with allergy appear to be more vulnerable to rhinovirus infections, however other studies have contradicted this. Rhinovirus infection affects the expression of co-stimulatory molecules and inflammatory cytokines. However, it remains unclear that the relevance between allergic status and rhinovirus infection. Therefore, in this study, we aimed to find out the susceptibility to rhinovirus infection and its effects on the expressions of co-stimulatory molecules and cytokines in patients with allergic rhinitis. Materials and Methods: Uncinate process tissues were obtained from 39 patients with allergy and 21 patients without allergy who underwent surgical management of endoscopic sinus surgery (ESS) due to chronic rhinosinusitis (CRS). The mucosa was infected with RVs, and RT-PCR and semi-nested PCR were used to confirm the rhinovirus infection. Real-time PCR was used to determine gene expression level of programmed cell death ligand 1 (PDL1), programmed cell death ligand 2 (PDL2), intracellular adhesion molecule 1 (ICAM-1), IFN-γ, IL-4, IL-5, and IL-10 in nasal mucosa tissues. Western blotting and immunohistochemistry were performed to evaluate the level of PDL1, PDL2, ICAM-1 and IL-10 protein in nasal mucosa tissues. Results: The RV infection rates were not significantly different between allergy and non-allergy group. In allergy group, compared to control tissues, RV infected tissues showed significantly elevated expression of PDL2, ICAM-1, IL-4 and IL-10. On the other hand, RV infection to tissues from non-allergy group increased levels of IL-4 and IL-5 compared to those of control tissues. In cases of PDL1 and IL-10, infected tissues from allergy group exhibit higher levels than those from non-allergy group. Interestingly, a high degree of correlation between PDL1 and IL-10 was seen in allergy group, but there was no definite correlation seen in non-allergy group. In cases of IL-4 and IL-5, infected tissues from non-allergy group exhibit higher levels than those from allergy group. There was no significant difference in expression of IFN-γ mRNA between two groups. Conclusion: Allergy and non-allergy subjects tend to have a similar degree of susceptibility to RV infection. This study suggests that enhanced PDL1 and IL-10 can suppress the immune response to RV infection, and this suppression process is more likely induce severe symptoms in allergic patients with rhinovirus. Furthermore, elevated levels of IL-4 and IL-5 in infected tissue from non-allergy group suggest that repeated rhinovirus infection history may cause Th2 biased environment.Contents Abstract ..................................................................... i Contents ................................................................... iv List of Tables and Figures ...................................... v List of abbreviations ............................................... vi Introduction .............................................................. 1 Materials & Methods ............................................... 4 Results .................................................................... 14 Discussion .............................................................. 20 References ............................................................. 26 Tables and Figures ................................................ 32 Abstract (Korean ) .................................................. 42 Acknowledgement .................................................. 45Maste