title: Serum S100A8 and S100A9 Enhance Innate Immune Responses in the Pathogenesis of Baker's Asthma.
abstract: BACKGROUND
  S100A8 and S100A9 can be produced by lipopolysaccharide-stimulated granulocytes and provoke an innate immune-mediated airway inflammation. Involvement of S100A8 and S100A9 has been implicated in asthma. To further understand the role of S100A8 and S100A9 during innate immune responses in baker's asthma, we investigated the associations of serum S100A8 and S100A9 with exposure to bakery allergens and polymorphisms of the Toll-like receptor 4 (TLR4) gene.
  
  
  METHODS
  Totally, 381 bakery workers and 100 unexposed healthy controls were recruited. Skin prick tests for bakery allergens were performed. Serum levels of S100A8, S100A9, myeloperoxidase (MPO), tumor necrosis factor (TNF)-α, and interleukin (IL)-8 were measured using ELISA. Predictive values of serum S100A8 and S100A9 in bakery workers were evaluated by receiver-operating characteristic (ROC) curves. Polymorphisms of TLR4 -2027Ax2192;G and -1608Tx2192;C were genotyped.
  
  
  RESULTS
  Higher serum levels of S100A8 and S100A9 were noted in bakery workers compared to the normal controls (p < 0.001); however, no significant differences were noted according to work-related symptoms. The area under the ROC curve of serum S100A8 was 0.886 for occupational exposure (p < 0.001). The TLR4 -1608CC genotype was significantly associated with a higher serum S100A8 level (p = 0.025). Serum S100A8 and S100A9 levels were correlated with serum levels of MPO (r = 0.396 and 0.189, respectively), TNF-α (r = 0.536 and 0.280, respectively), and IL-8 (r = 0.540 and 0.205, respectively; p < 0.001 for all).
  
  
  CONCLUSIONS
  S100A8 and S100A9 are involved in innate immune responses under the regulation of TLR4 polymorphisms in baker's asthma pathogenesis. Serum S100A8 could be a potential biomarker for predicting occupational exposure to wheat flour in bakery workers.
authors.affiliation: Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, South Korea.
authors.forename: Duy Le
authors.initials: DL
authors.lastname: Pham
authors.forename: Moon-Guyng
authors.initials: MG
authors.lastname: Yoon
authors.forename: Ga-Young
authors.initials: GY
authors.lastname: Ban
authors.forename: Seung-Hyun
authors.initials: SH
authors.lastname: Kim
authors.forename: Mi-Ae
authors.initials: MA
authors.lastname: Kim
authors.forename: Young-Min
authors.initials: YM
authors.lastname: Ye
authors.forename: Yoo Seob
authors.initials: YS
authors.lastname: Shin
authors.forename: Hae-Sim
authors.initials: HS
authors.lastname: Park
mesh_terms: D000328:Adult; D000485:Allergens; D059366:Asthma, Occupational / Q000097:blood* / Q000235:genetics / Q000276:immunology; D040501:Calgranulin A / Q000097:blood* / Q000276:immunology; D040502:Calgranulin B / Q000097:blood* / Q000276:immunology; D005260:Female; D005433:Flour; D006801:Humans; D007113:Immunity, Innate; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D016209:Interleukin-8 / Q000097:blood; D008297:Male; D009195:Peroxidase / Q000097:blood; D020641:Polymorphism, Single Nucleotide; D056910:Republic of Korea; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000276:immunology; D014908:Triticum / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D055815:Young Adult
chemical_list: D000485:Allergens; C508606:CXCL8 protein, human; D040501:Calgranulin A; D040502:Calgranulin B; D007074:Immunoglobulin G; D016209:Interleukin-8; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D007073:Immunoglobulin E; D009195:Peroxidase