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.

Background: Short palate, lung, and nasal epithelium clone 1 (SPLUNC1) protein is an airway epithelial cell–derived molecule exerting host defense against pathogen. However, the function and regulation of SPLUNC1 in nasal epithelial cells are still unclear. Chronic rhinosinusitis with nasal polyps (CRSwNPs) is a disorder characterized by eosinophilic Th2 inflammation and frequent microbial colonization. The pathogenesis has been postulated as a disturbed mucosal immune response. This study investigates the SPLUNC1 expression of nasal polyp epithelial cells in air–liquid interface (ALI) culture and after treating with Th2 inflammatory cytokines IL-13. Methods: Human nasal polyp epithelial cells isolated from patients with CRSwNPs were put in different cell culture models at days 0 and 21 and were assessed for expression of SPLUNC1 by microarray. Cultured cells in ALI plus retinoic acid (ALI + RA) model were then incubated with 0, 1, 10, and 100 ng/mL human recombinant IL-13 for up to 5 days. The expression of SPLUNC1 was assessed by real-time quantitative polymerase chain reaction (RT-Q-PCR), reverse-transcriptase PCR (RT-PCR) and Western blot analysis. Results: ALI + RA culture model harvesting ciliary differentiated nasal epithelial cells constitutively expressed high levels of SPLUNC1. In contrast, SPLUNC1 is reduced under classic submerged single layer culture. SPLUNC1 is also dose-responsively down-regulated after incubation with IL-13. Conclusions: A microenvironmental milieu containing IL-13 may be detrimental to the host innate immunity response, at least in part, through the inhibition of SPLUNC1 production.

Chronic rhinosinusitis (CRS) is one of the most common causes of inflammation of the olfactory system, warranting investigation of the link between chronic inflammation and the loss of olfactory function. Type 2 inflammation is closely related to the clinical features and disease mechanisms of olfactory dysfunction secondary to CRS. Patients with eosinophilic CRS, aspirin-exacerbated respiratory disease, and central compartment atopic disease report increased olfactory dysfunction. Increased levels of interleukin-(IL-)2, IL-5, IL-6, IL-10, and IL-13 in the mucus from the olfactory slit have been reported to be associated with reduced olfactory test scores. The influence of several cytokines and signaling transduction pathways, including tumor necrosis factor-α, nuclear factor-κB, and c-Jun N-terminal kinases, on olfactory signal processing and neurogenesis has been demonstrated. Corticosteroids are the mainstay treatment for olfactory dysfunction secondary to CRS. Successful olfaction recovery was recently demonstrated in clinical trials of biotherapeutics, including omalizumab and dupilumab, although the treatment effect may diminish gradually after stopping the use of the medications. Future studies are required to relate the complex mechanisms underlying chronic inflammation in CRS to dysfunction of the olfactory system.