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Background: Nasal epithelial cells are the first site of encounter of the influenza virus, and their innate immune response might define subsequent inflammatory direction. Aims/objectives: We used metabolomics analysis to identify metabolic changes and the regulation of inflammatory cytokines in nasal epithelial cells upon influenza virus infection. Material and methods: We cultured nasal epithelial cells using air-liquid interface (ALI) model. Influenza virus (PR8) infection followed by metabolomic analysis was performed. Furthermore, cytokine expression was analyzed by cytokine array and RT-qPCR. Results: Metabolomic analysis revealed depletion of the tryptophan and accumulation of its metabolite, kynurenine, within 48 h. The major enzyme involved in the tryptophan metabolic pathway, indoleamine 2,3-dioxygenase (IDO), was overexpressed after infection. Cytokine expression array after infection showed increased levels of IL-1α, CCL2, IL-6, CXCL10, CCL5, and CXCL11, and after using 1-methyltryptophan (1-MT) as inhibitor, the expression levels of IL-6 and G-CSF were reduced. Conclusions and significance: Viral infection results in depletion of tryptophan and accumulation of kynurenine via increased cellular IDO activity. Inhibition of IDO activity or replenishment of tryptophan by local application may be a good therapeutic strategy for limiting the initial damage caused by influenza virus in nasal epithelial cells.

Conclusions: Nasal epithelial cells are constitutively equipped with all Toll-like receptors (TLRs) which are essential for innate immunity. Both mRNA and protein levels of TLR3 expression increased in more differentiated nasal epithelial cells. Considering that the ligand for TLR3 is viral dsRNA, this result is in good accordance with previous reports demonstrating that more differentiated airway epithelial cells have increased resistance to rhinovirus infection., Objective: Nasal epithelial cells use innate immune responses to combat inspired potential pathogens. TLRs are receptors that recognize pathogen-associated molecular patterns of microbes. Therefore, we investigated the expression of TLRs in cultured nasal epithelial cells obtained from nasal polyps., Materials and Methods: Submerged single layer (SSL) and air-liquid interface (ALI) nasal epithelial cell cultures with or without 10(-7) M retinoid acid (+/- RA) were created., Results: ALI + RA culture developed ciliary differentiation as observed by light and scanning electron microscopic examination in 3 weeks. It had higher interleukin (IL)-8 basal secretion (21.9 vs 0.82-1.45 ng/ml) and transepithelial potential (-20.4 mV). TLR1-10 mRNA expression in cultured nasal epithelial cells was determined by RT-PCR. Only TLR3 mRNA significantly increased at day 20 vs day 1 (n=5, p=0.02) in ALI + RA cell culture. Higher TLR3 protein was also expressed at day 20 in ALI + RA cell culture but not in SSL culture by western blotting.

Objectives: Endoscopic endonasal transsphenoidal adenomectomy (TSA) is the most frequently performed skull base surgery, and researchers have recently focused on preserving nasal function. The endoscopic transseptal approach is a promising procedure due to its reduced injury to the nasal mucosa; however, there are no studies comparing rhinological and neurosurgical outcomes concurrently with the standard endoscopic transnasal approach. Therefore, we conducted this study to investigate whether the transseptal approach could reduce nasal morbidities with comparable neurosurgical outcomes. Methods: We retrospectively reviewed 25 patients who underwent endoscopic endonasal transseptal TSA for pituitary adenoma without encasement of internal carotid artery from January 2019 to December 2020. Another 25 patients who received transnasal approach from January 2017 to December 2018 were selected as controls. Patients with diseases affecting the nasal cavity/olfaction or usage of a nasoseptal flap were excluded for a better comparison of the two procedures. We collected data from radiological studies, endocrine studies, endoscopic evaluations, 22‐item sinonasal outcome tests (SNOT‐22) and Top International Biotech Smell Identification Test (TIBSIT) for comparison. Results: Lower postoperative SNOT‐22 and Lund‐Kennedy endoscopic scores were observed in the transseptal group. The effect size of differences were classified as large effect (The absolute value of Cohen's d > 0.8). Nevertheless, the TIBSIT scores were not significantly different. The rates of gross total resection, recovery of hormonal abnormalities, and complications were not significantly different. After controlling possible confounding factors using multivariate analysis, the endoscopic transseptal approach remained an independent factor for lower SNOT‐22 scores and Lund‐Kennedy endoscopic scores. Conclusions: The endoscopic transseptal approach provides improved recovery of nasal mucosa and intact olfaction without compromising neurosurgical outcomes. Level of Evidence: 2b. [ABSTRACT FROM AUTHOR]