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.

Keywords:
Fungus, Epithelial cell, Protease, Toll-like receptor
1.
Ponikau JU, Sherris DA, Kern EB, et al: The diagnosis and incidence of allergic fungal sinusitis. Mayo Clin Proc 1999;74:877–884.
2.
Bachert C, van Zele T, Gevaert P, et al: Superantigens and nasal polyps. Curr Allergy Asthma Rep 2003;3:523–531.
3.
Millar JW, Hohnston A, Lamb D: Allergic aspergillosis of the maxillary sinuses. Proc Scott Thor Soc 1981;36:710.
4.
Kauffman HF, Tomee JF, van der Riet MA, et al: Protease-dependent activation of epithelial cells by fungal allergens leads to morphologic changes and cytokine production. J Allergy Clin Immunol 2000;105:1185–1193.
5.
Akbari O, DeKruyff RH, Kaisho T: Toll-like receptors: critical proteins linking innate and acquired immunity. Nat Immun 2001;2:675–680.
6.
Dong Z, Yang Z, Wang Z: Expression of TLR2 and TLR4 messenger RNA in the epithelial cells of the nasal airway. Am J Rhinol 2005;19:236–239.
7.
Claeys S, Van Hoecke H, Holtappels G, et al: Nasal polyps in patients with and without cystic fibrosis: a differentiation by innate markers and inflammatory mediators. Clin Exp Allergy 2005;35:467–472.
8.
Xaubet A, Mullol J, Lopez E, et al: Comparison of the role of nasal polyp and normal nasal mucosal epithelial cells on in vitro eosinophil survival mediation by GM-CSF and inhibition by dexamethasone. Clin Exp Allergy 1994;24:307–317.
9.
Roca-Ferrer J, Mullol J, Lopez E, et al: Effect of topical anti-inflammatory drugs on epithelial cell induced eosinophil survival and GM-CSF secretion. Eur Respir J 1997;10:1489–1495.
10.
Borger P, Koeter GH, Timmerman JAB, et al: Proteases from Aspergillus fumigatus induce interleukin (IL)-6 and IL-8 production in airway epithelial cell lines by transcriptional mechanisms. J Infec Dis 1999;180:1267–1274.
11.
Kurup VP, Banerjee B: Fungal allergens and peptide epitopes. Peptides 2000;21:589–599.
12.
Shin SH, Lee YH, Jeon CH: Protease-dependent activation of nasal polyp epithelial cells by airborne fungi leads to migration of eosinophils and neutrophils. Acta Otolaryngol 2006;126:1286–1294.
13.
Takeda K, Kaisho T, Akira S: Toll-like receptors. Annu Rev Immunol 2003;21:335–376.
14.
Rakoff-Nahoum S, Paglino J, Eslami-Varzaneh F, et al: Recognition of commensal microflora by toll-like receptors is required for intestinal homeostasis. Cell 2004;118:229–241.
15.
Janssens S, Beyaert R: Role of toll-like receptors in pathogen recognition. Clin Microbiol Rev 2003;16:637–646.
16.
Veindl G, Naglik JR, Kaesler S, et al: Human epithelial cells establish direct antifungal defense through TLR4-mediated signaling. J Clin Invest 2007;117:3664–3672.
17.
Dong Z, Yang Z, Wang C: Expression of TLR2 and TLR4 messenger RNA in the epithelial cells of the nasal airway. Am J Rhinol 2005;19:236–239.
18.
Pitzurra L, Bellocchio S, Nocentini A, et al: Antifungal immune reactivity in nasal polyposis. Infect Immun 2004;72:7275–7281.
19.
Wang J, Matsukura S, Watanabe S, et al: Involvement of Toll-like receptors in the immune response of nasal polyp epithelial cells. Clin Immunol 2007;124:345–352.
20.
Netea MG, Van Der Graaf CA, Vonk AG, et al: The role of toll-like receptor (TLR) 2 and TLR4 in the host defense against disseminated candidiasis. J Infec Dis 2002;185:1483–1489.
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2010
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