title: Chitin stimulates expression of acidic mammalian chitinase and eotaxin-3 by human sinonasal epithelial cells in vitro.
abstract: BACKGROUND
  Sinonasal epithelial cells participate in host defense by initiating innate immune mechanisms against potential pathogens. Antimicrobial innate mechanisms have been shown to involve Th1-like inflammatory responses. Although epithelial cells can also be induced by Th2 cytokines to express proeosinophilic mediators, no environmental agents have been identified that promote this effect.
  
  
  METHODS
  Human sinonasal epithelial cells from patients with chronic rhinosinusitis with nasal polyps (CRSwNPs) and controls were harvested and grown in primary culture. Cell cultures were exposed to a range of concentrations of chitin for 24 hours, and mRNA for acidic mammalian chitinase (AMCase), eotaxin-3, and thymic stromal-derived lymphopoietin (TSLP) were assessed. Other cultures were exposed to interleukin 4 (IL- 4) alone and in combination with dust-mite antigen (DMA) for 36 hours. Extracted mRNA and cell culture supernatant were analyzed for expression of AMCase and eotaxin-3.
  
  
  RESULTS
  Chitin induced a dose-dependent expression of AMCase and eotaxin-3 mRNA but not TSLP. Patients with recalcitrant CRSwNPs showed lower baseline expression of AMCase when compared with treatment-responsive CRSwNP and less induction of AMCase expression by chitin. DMA did not directly induce expression of AMCase or eotaxin-3. Expression of eotaxin-3 was stimulated by IL-4 and further enhanced with the addition of DMA. Levels of AMCase were not significantly affected by either IL-4 or DMA exposure. In some cases, the combination of IL-4 and DMA was able to induce AMCase expression in cell cultures not producing AMCase at baseline.
  
  
  CONCLUSIONS
  The abundant biopolymer chitin appears to be recognized by a yet uncharacterized receptor on sinonasal epithelial cells. Chitin stimulates production of AMCase and eotaxin-3, two pro-Th2 effector proteins. This finding suggests the existence of a novel innate immune pathway for local defense against chitin-containing organisms in the sinonasal tract. Dysregulation of this function could precipitate or exacerbate Th2 inflammation, potentially acting as an underlying factor in recalcitrant CRSwNP.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Ashley
authors.initials: A
authors.lastname: Lalaker
authors.forename: Louis
authors.initials: L
authors.lastname: Nkrumah
authors.forename: Won-Kyung
authors.initials: WK
authors.lastname: Lee
authors.forename: Murugappan
authors.initials: M
authors.lastname: Ramanathan
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Lane
mesh_terms: D016887:Cardiopulmonary Resuscitation; D002478:Cells, Cultured; D000075906:Chemokine CCL26; D019742:Chemokines, CC / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics*; D002686:Chitin / Q000494:pharmacology*; D002688:Chitinases / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics*; D004804:Eosinophils; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D015521:Ethmoid Sinusitis / Q000235:genetics / Q000276:immunology / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D009297:Nasal Mucosa / Q000378:metabolism* / Q000473:pathology; D012313:RNA / Q000235:genetics*; D012220:Rhinitis / Q000235:genetics / Q000276:immunology / Q000473:pathology; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology
chemical_list: C120429:CCL26 protein, human; D000075906:Chemokine CCL26; D019742:Chemokines, CC; D002686:Chitin; D012313:RNA; C499254:CHIA protein, human; D002688:Chitinases