171 Augmentation of cxcl10 Expression in Nasal Fibroblasts Derived from Patients With Recalcitrant Chronic Rhinosinusitis Associated With Bronchial Asthma

171 Augmentation of cxcl10 Expression in Nasal Fibroblasts Derived from Patients With Recalcitrant Chronic Rhinosinusitis Associated With Bronchial Asthma Mamoru Yoshikawa, MD, Tsuyoshi Yoshimura, MD, Daiya Asaka, MD, Naoko Okada, PhD, Hirohisa Saito, MD, PhD, and Hiroshi Moriyama, MD. Department of Otorhinolaryngology, Jikei University School of Medicine, Tokyo, Japan; National Research Institute for Child Health & Development, Tokyo, Japan. Background: The prevalence of chronic rhinosinusitis (CRS) that is refractory to traditional therapy appears to be increasing, and CRS that is refractory to traditional therapy tends to be associated with bronchial asthma (BA), especially, aspirin-intolerant asthma (AIA). After viral infections, patients with CRS associated with BA usually experience exacerbations of their CRS symptoms, including nasal polyposis, in comparison with CRS patients without BA. Alternatively tissue fibroblasts as an important component of the epithelial mesenchymal trophic unit play a key role in maintaining tissue homeostasis and may also have the potential to contribute to disease pathogenesis through their contribution to inflammatory responses. On the basis of these findings, we hypothesized that CRS patients with BA are more susceptible to inflammation of the nasal and paranasal mucosa depending on the antiviral response of nasal fibroblasts. Methods: Tissue specimens were obtained from the nasal polyps of 3 groups of CRS patients, a group that did not have BA (CRS-NA group), a group with aspirin-tolerant asthma (CRS-ATA group), and a group with AIA (CRS-AIA group). Nasal polyp fibroblasts (NPFs) were isolated from the specimens and stimulated with poly I: C. By using a DNA microarray and performing a hierarchical clustering analysis we were able to identify a cluster containing genes that were up-regulated after poly I: C stimulation. To confirm the results of the analysis data, we used quantitative real-time PCR (qRT-PCR) and an enzyme-linked immunoadsorbent assay (ELISA). Results: Expression of IFN-inducible protein 10 (IP-10)/CXCL10 transcript was higher in the NPFs of the CRS-AIA group and CRS-ATA group than in the CRS-NA group and control group. These findings were confirmed by qRT-PCR and ELISA. Conclusions: The results of this study suggest that the increased poly I:Cinduced CXCL10 expression in NPFs derived from the CRS patients with BA is involved in susceptible to T helper (Th)1-type immune response in the nasal and paranasal mucosa by viral infection compared with CRS patients without BA.