title: Role of TLRs in the production of chemical mediators in nasal polyp fibroblasts by fungi.
abstract: OBJECTIVE
  Fibroblasts are major supporting cells in nasal mucosa and can induce inflammatory process with recruitment of inflammatory cells. Airborne fungi have been suggested as an etiologic factor of chronic rhinosinusitis (CRS). The aim of this study was to investigate the interaction between airborne fungi and pattern recognition receptors (PRRs) in nasal fibroblasts.
  
  
  METHODS
  Primary nasal polyp fibroblasts were cultured with Alternaria and Aspergillus for 48h. To determine the production of chemical mediators interleukine-6 (IL-6), IL-8, granulocyte-macrophage colony stimulating factor (GM-CSF), eotaxin, and regulated on activation normal T expressed and secreted (RANTES) were measured with enzyme immunoassay methods. PRRs for toll-like receptors (TLRs) and protease-activated receptors (PARs) mRNA were determined with reverse transcription polymerase chain reaction (RT-PCR). To determine the role of PRRs, fibroblasts were treated with small interfering RNA (siRNA).
  
  
  RESULTS
  IL-6 and IL-8 productions were significantly increased by 50 and 100μg/ml of Alternaria. However, GM-CSF, eotaxin, and RANTES productions did not change. Aspergillus did not influence the production of chemical mediators from nasal polyp fibroblasts. TLR2 and TLR5 mRNA expressions were significantly increased by fungi and these two TLRs were associated with the production of IL-6 and IL-8.
  
  
  CONCLUSIONS
  Alternaria interacts as a pathogen-associated molecular pattern with the PRRs, such as TLR2 and TLR5, which induce the production of inflammatory chemical mediators from nasal polyp fibroblasts. Airborne fungi enhance the innate immune defense mechanism and may be associated with the pathogenesis of nasal inflammatory diseases.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, School of Medicine, Catholic University of Daegu, Daegu, Republic of Korea. Electronic address: hsseung@cu.ac.kr.
authors.forename: Seung-Heon
authors.initials: SH
authors.lastname: Shin
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, School of Medicine, Catholic University of Daegu, Daegu, Republic of Korea.
authors.forename: Mi-Kyung
authors.initials: MK
authors.lastname: Ye
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, School of Medicine, Catholic University of Daegu, Daegu, Republic of Korea.
authors.forename: Yee-Hyuk
authors.initials: YH
authors.lastname: Kim
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, School of Medicine, Catholic University of Daegu, Daegu, Republic of Korea.
authors.forename: Jeong-Kyu
authors.initials: JK
authors.lastname: Kim
mesh_terms: D000328:Adult; D000528:Alternaria; D001230:Aspergillus; D002478:Cells, Cultured; D018946:Chemokine CCL5 / Q000378:metabolism; D018925:Chemokines / Q000378:metabolism; D002908:Chronic Disease; D005260:Female; D005347:Fibroblasts / Q000378:metabolism*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009181:Mycoses / Q000235:genetics* / Q000378:metabolism / Q000382:microbiology; D009298:Nasal Polyps / Q000235:genetics* / Q000378:metabolism / Q000382:microbiology; D012333:RNA, Messenger / Q000378:metabolism*; D034741:RNA, Small Interfering; D051192:Receptors, Pattern Recognition / Q000235:genetics* / Q000378:metabolism; D044462:Receptors, Proteinase-Activated / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012220:Rhinitis / Q000235:genetics / Q000378:metabolism / Q000382:microbiology; D012852:Sinusitis / Q000235:genetics / Q000378:metabolism / Q000382:microbiology; D051193:Toll-Like Receptors / Q000378:metabolism*
chemical_list: C483024:CCL5 protein, human; C508606:CXCL8 protein, human; D018946:Chemokine CCL5; D018925:Chemokines; C508600:IL6 protein, human; D015850:Interleukin-6; D016209:Interleukin-8; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D051192:Receptors, Pattern Recognition; D044462:Receptors, Proteinase-Activated; D051193:Toll-Like Receptors; D016178:Granulocyte-Macrophage Colony-Stimulating Factor
keywords: Cytokine; Fungus; Nasal fibroblast; Toll-like receptor