title: Airway Goblet Cells Secrete Pro-Inflammatory Cytokines, Chemokines, and Growth Factors.
abstract: BACKGROUND
  IL-13 is a T-helper cell type 2 cytokine that plays an important role in the pathogenesis of asthma. IL-13 exposure for 14 days transforms cultured normal human bronchial epithelial cells to a goblet cell phenotype. We hypothesized that goblet cells would have a different pattern of cytokine secretion than ciliated airway cells.
  
  
  METHODS
  Normal human bronchial epithelial cells were grown for 14 days at an air-liquid interface with IL-13 to produce a goblet cell phenotype (n = 4) or with phosphate-buffered saline to produce ciliated cells (n = 4). Ciliated cells were also acutely exposed to IL-13 for 24 h (n = 4). Apical (air side) and basolateral medium was collected, and a multiplex immunoassay of 27 cytokines and inflammatory mediators was performed. The pattern of mediator secretion was then compared.
  
  
  RESULTS
  The goblet cell phenotype secreted greater amounts of proinflammatory cytokines and mediators than ciliated cells and, for the most part, apical secretion was greater than secretion into the basolateral medium. Apical IL-4, IL-5 (P < .0033), and IL-9 (P < .001) and basolateral IL-9, IL-13 (P < .0001), eotaxin, IL-17 (P < .0033), basic fibroblast growth factor (P < .001), and vascular endothelial growth factor (P < .0001) were secreted in greater amounts from goblet cells than from ciliated cells. IL-8 was secreted in higher concentration in both apical (P < .0001) and basolateral (P < .0033) compartments from the goblet cells. Ciliated cells exposed to IL-13 for just 24 h had modestly increased apical IL-8 secretions (P < .0033), but there was no increase in other cytokines.
  
  
  CONCLUSIONS
  Inflammatory mediators released from goblet cells may act in an autocrine and paracrine manner to enhance inflammation in diseases such as asthma in which there is increased IL-13 and goblet cell hyperplasia.
authors.affiliation: Division of Internal Medicine, Municipal Shinetsu Hospital, Shinano-machi, Nagano, Japan; Department of Pediatrics, Children's Hospital of Richmond at Virginia Commonwealth University School of Medicine, Richmond, Virginia. Electronic address: ttanabe16@gmail.com.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Tanabe
authors.affiliation: Department of Pediatrics, Children's Hospital of Richmond at Virginia Commonwealth University School of Medicine, Richmond, Virginia.
authors.forename: Bruce K
authors.initials: BK
authors.lastname: Rubin
mesh_terms: D001980:Bronchi / Q000166:cytology*; D002923:Cilia; D016207:Cytokines / Q000378:metabolism*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D020397:Goblet Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007249:Inflammation; D018793:Interleukin-13 / Q000378:metabolism / Q000494:pharmacology*; D020381:Interleukin-17 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D015848:Interleukin-5 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D016906:Interleukin-9 / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: C508606:CXCL8 protein, human; D016207:Cytokines; C508598:IL4 protein, human; C508599:IL5 protein, human; C508607:IL9 protein, human; D018793:Interleukin-13; D020381:Interleukin-17; D015848:Interleukin-5; D016209:Interleukin-8; D016906:Interleukin-9; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D015847:Interleukin-4
keywords: airway inflammation; allergic asthma; asthma; cilia; immunology asthma