title: Cigarette smoke promotes eosinophilic inflammation, airway remodeling, and nasal polyps in a murine polyp model.
abstract: BACKGROUND
  Exposure to cigarette smoking (CS) is a major risk factor for airway inflammation. However, little is known about the effects of CS exposure on eosinophilic rhinosinusitis with nasal polyps (ERSwNPs). Histopathological and molecular studies were performed to investigate its effects using a murine model of ERSwNPs.
  
  
  METHODS
  Mice were assigned to one of the following four groups (n = 8 for each group): control group, CS exposure (CS group), ERSwNP (ERS group), and ERSwNPs exposed to CS (ERS + CS group). Histopathological changes were investigated using various stains, including hematoxylin and eosin for inflammation and polyp-like lesions, Sirius red for eosinophils, toluidine blue for mast cells, Alcian blue for goblet cells, and Masson's trichrome stain for collagen fibers. mRNA expression of cytokines from nasal mucosae was measured. Serum IgE and systemic cytokine levels were measured by enzyme-linked immunosorbent assays. The expression of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor (HIF) 1-alpha was evaluated by immunohistochemical staining.
  
  
  RESULTS
  The ERS + CS group showed more severe symptoms, increased the number of polyp-like lesions, infiltration of eosinophils, goblet cell hyperplasia, and subepithelial fibrosis, compared with the ERS group. Additionally, mRNA expressions of IL-4 and IL-17A were up-regulated in ERS + CS group and higher levels of IL-4, IL-6, IL-17A, and interferon gamma from splenocytes were observed significantly in the ERS + CS group compared with the ERS group. In the ERSwNP murine model, exposure to CS enhanced the expression of VEGF and HIF-1-alpha in nasal epithelial cells.
  
  
  CONCLUSIONS
  Chronic exposure to CS aggravated eosinophilic inflammation and promoted airway remodeling and nasal polyp formation in a murine model of ERSwNPs. The underlying mechanism might involve up-regulated expression of VEGF and HIF-1-alpha.
authors: Department of Otorhinolaryngology, Dankook University College of Medicine, Chonan, South Korea.
authors: Ki-Il
authors: KI
authors: Lee
authors: Dae Woo
authors: DW
authors: Kim
authors: Eun Hee
authors: EH
authors: Kim
authors: Jie Hye
authors: JH
authors: Kim
authors: Ramachandran
authors: R
authors: Samivel
authors: Ji Eun
authors: JE
authors: Kwon
authors: Jin-Chul
authors: JC
authors: Ahn
authors: Young-Jun
authors: YJ
authors: Chung
authors: Ji-Hun
authors: JH
authors: Mo
mesh_terms: D056151:Airway Remodeling; D000818:Animals; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004804:Eosinophils / Q000276:immunology*; D005355:Fibrosis; D020397:Goblet Cells / Q000473:pathology*; D006801:Humans; D006965:Hyperplasia; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D007073:Immunoglobulin E / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D009297:Nasal Mucosa / Q000276:immunology*; D009298:Nasal Polyps / Q000276:immunology* / Q000473:pathology; D012907:Smoking / Q000009:adverse effects*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D016207:Cytokines; C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D042461:Vascular Endothelial Growth Factor A; D007073:Immunoglobulin E