title: Regulatory effect of TLR3 signaling on staphylococcal enterotoxin-induced IL-5, IL-13, IL-17A and IFN-γ production in chronic rhinosinusitis with nasal polyps.
abstract: BACKGROUND
  Toll-like receptor 3 (TLR3) is expressed in upper airways, however, little is known regarding whether Toll-like receptor 3 (TLR3) signals exert a regulatory effect on the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP), especially on eosinophilic inflammation. We sought to investigate the effect of Poly(IC), the ligand for TLR3, on cytokine production by dispersed nasal polyp cells (DNPCs).
  
  
  METHODS
  DNPCs were pretreated with or without Poly(IC), and were then cultured in the presence or absence of staphylococcal enterotoxin B (SEB), following which the levels of IL-5, IL-10, IL-13, IL-17A and interferon (IFN)-γ in the supernatant were measured. To determine the involvement of IL-10 and cyclooxygenase in Poly(IC)-mediated signaling, DNPCs were treated with anti-IL-10 monoclonal antibody and diclofenac, the cyclooxygenase inhibitor, respectively. Poly(IC)-induced prostaglandin E2 (PGE2) production was also determined.
  
  
  RESULTS
  Exposure to Poly(IC) induced a significant production of IL-10, but not of IL-5, IL-13, IL-17A or IFN-γ by DNPCs. Pretreatment with Poly(IC) dose-dependently inhibited SEB-induced IL-5, IL-13 and IL-17A, but not IFN-γ production. Neutralization of IL-10 significantly abrogated the inhibitory effect of Poly(IC). Treatment with diclofenac also abrogated the inhibitory effect of Poly(IC) on SEB-induced IL-5 and IL-13 production. However, unlike exposure of diclofenac-treated DNPCs to lipopolysaccharide, the ligand for TLR4, exposure of these cells to Poly(IC) did not enhance IL-5 or IL-13 production. Poly(IC) did not significantly increase PGE2 production by DNPCs.
  
  
  CONCLUSIONS
  These results suggest that TLR3 signaling regulates eosinophilia-associated cytokine production in CRSwNP, at least in part, via IL-10 production.
authors.affiliation: Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan. Electronic address: mokano@cc.okayama-u.ac.jp.
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Okano
authors.affiliation: Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Tazuko
authors.initials: T
authors.lastname: Fujiwara
authors.affiliation: Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Shin
authors.initials: S
authors.lastname: Kariya
authors.affiliation: Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Takaya
authors.initials: T
authors.lastname: Higaki
authors.affiliation: Department of Otorhinolaryngology, Kagawa Rosai Hospital, Kagawa, Japan.
authors.forename: Sei-ichiro
authors.initials: S
authors.lastname: Makihara
authors.affiliation: Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Takenori
authors.initials: T
authors.lastname: Haruna
authors.affiliation: Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Noyama
authors.affiliation: Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Takahisa
authors.initials: T
authors.lastname: Koyama
authors.affiliation: Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Ryotaro
authors.initials: R
authors.lastname: Omichi
authors.affiliation: Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Yorihisa
authors.initials: Y
authors.lastname: Orita
authors.affiliation: Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Miki
authors.affiliation: Department of Otorhinolaryngology, Kagawa Prefectural Central Hospital, Kagawa, Japan.
authors.forename: Kengo
authors.initials: K
authors.lastname: Kanai
authors.affiliation: Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Nishizaki
mesh_terms: D000328:Adult; D000368:Aged; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D004768:Enterotoxins / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D018793:Interleukin-13 / Q000096:biosynthesis; D020381:Interleukin-17 / Q000096:biosynthesis; D015848:Interleukin-5 / Q000096:biosynthesis; D008875:Middle Aged; D009298:Nasal Polyps / Q000150:complications*; D011070:Poly I-C / Q000494:pharmacology; D012220:Rhinitis / Q000150:complications* / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction; D012852:Sinusitis / Q000150:complications* / Q000276:immunology / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D051196:Toll-Like Receptor 3 / Q000378:metabolism*; D055815:Young Adult
chemical_list: D016207:Cytokines; D004768:Enterotoxins; D018793:Interleukin-13; D020381:Interleukin-17; D015848:Interleukin-5; D051196:Toll-Like Receptor 3; C031818:enterotoxin B, staphylococcal; D007371:Interferon-gamma; D011070:Poly I-C
keywords: Chronic rhinosinusitis with nasal polyps; IL-10; IL-5; Poly(IC); Toll-like receptor