Airborne Fungi Induce Nasal Polyp Epithelial Cell Activation and Toll-Like Receptor Expression

Abstract

Background: The nasal epithelium is the first barrier encountered by airborne allergens and is an active participant in airway inflammation. Fungi have been increasingly recognized as important pathogens in sinusitis and airway diseases. The aim of the study was to evaluate fungal protease activity during cytokine production in nasal polyp epithelial cells and to determine the expression of Toll-like receptor (TLR) mRNA by fungi. Methods: Nasal polyp epithelial cells were obtained from patients and stimulated with Alternaria and Aspergillus. Interleukin-8 (IL-8) and granulocyte macrophage colony-stimulating factor (GM-CSF) were measured to determine the activation of epithelial cells. Reverse transcriptase polymerase chain reaction for the TLR mRNA expression of the nasal epithelial cells was performed. Cytokine production was inhibited with protease inhibitors and anti-human TLR antibodies. Results: The fungi enhanced the production of IL-8 and GM-CSF from nasal epithelial cells. When nasal epithelial cells were activated by the fungi, TLR2, TLR3 and TLR4 mRNAs were more strongly expressed than in the nonactivated cells. Cytokine production was inhibited by protease inhibitors and anti-human TLR4 antibodies. Conclusions: The results of this study showed that fungi interacted with nasal epithelial cells and enhanced the production of cytokines and TLR mRNA expression. The cytokine production was related to the protease in fungi and TLR4.

Effect of β‐glucan on MUC4 and MUC5B expression in human airway epithelial cells

“…regulation of the innate and adaptive immune response. [17][18][19][20] The pattern of TLR expression has been studied in many different type of cells. TLR2 and TLR4 mRNA have been found to be expressed in the nasal epithelial cells and these 2 genes have been reported to be significantly higher in chronic rhinosinusitis.…”

“…19 In addition, TLR4 was reported to contribute to airborne fungi-induced production of interleukin-8 and granulocyte-macrophage colony-stimulating factor in nasal polyp epithelial cells. 20 However, the effects of β-glucan on the productions of major airway mucins and the exact mechanisms related with TLRs have not been determined in human airway epithelial cells. Therefore, this study was conducted to determine whether β-glucan regulates the expressions of major airway mucin genes and to investigate the signaling pathway responsible for β-glucan-induced mucin production in human airway epithelial cells.…”

Bee Venom at Different Concentrations Modulates the Aeroallergen-Induced Activation of Nasal Polyp Epithelial Cells

“…The inhibition of chemical mediator production by BV was different depending on the kinds of allergen or stimulants. Although we cannot explain the exact cause of these discrepancies, these stimulants may activate nasal epithelial cells using different pathophysiologic mechanisms through receptors including G-protein-coupled receptors, toll-like receptors or protease-activated receptors or through various kinds of signal pathway [10,12,14].…”

“…Lipopolysaccharide (LPS; 10 μg/ml) was used as positive control. In our previous experiments with NPECs, maximal cytokine production was found at 50 μg/ml of Alternaria and 25 μg/ml of Aspergillus, DP and DF, the same concentration of these allergens were used currently [11,12]. After 24 h of incubation, the supernatants and epithelial cells were harvested and stored at -70°C until they were assayed.…”

Gene-environment interaction between Toll-like receptor 4 and mold exposure in the development of atopic dermatitis in preschool children

“…21,22) Several studies showed the associations that inflammatory responses by molds are mediated via TLR4. 23,24) However, it is not known whether interactions between TLR4 and mold have an impact on the development of allergic diseases, including AD.…”