title: The Chronic and Short-Term Effects of Gefinitib on Airway Remodeling and Inflammation in a Mouse Model of Asthma.
abstract: BACKGROUND
  Asthma is a complex and heterogeneous chronic inflammatory disorder which is characterized by airway remodeling and airway inflammation, including goblet cell and airway smooth muscle cell hyperplasia, mucus hypersecretion and eosinophils infiltration. Epidermal growth factor receptor (EGFR) plays an important role in goblet cell hyperplasia and mucus hypersecretion. We aimed to investigate the effects of gefitinib, an EGFR inhibitor, on ovalbumin (OVA)-induced airway remodeling and inflammation of a mouse model of asthma.
  
  
  METHODS
  Pathological changes of OVA sensitization of BALB/c mice were measured by H&amp;E and PAS staining; pEGFR, Bcl-2 and Bax expression was measured by western blot; ELISA was used to measure the level of muc5ac, IL-13 and IFN-x03B3;; TUNEL staining was used to detect goblet cell apoptosis.
  
  
  RESULTS
  At the present study, H&amp;E and PAS staining showed that mice pretreated with gefinitib developed fewer pathological changes compared with asthmatic mice and gefinitib treatment asthmatic mice, such as a remarkable reduction in airway inflammation, goblet cell and airway smooth muscle cell hyperplasia. Chronic gefitinib treatment or short-term gefitinib treatment significant down-regulate the expression of pEGFR compared with asthma group. Also, chronic gefitinib treatment markedly decreased the levels of muc5ac and IL-13 in BALF, whereas the level of IFN-x03B3; did not change obviously. TUNEL staining showed that the goblet cell apoptosis rate was much higher in the short-term gefinitib treatment group compared with the asthma and chronic gefitinib treatment group which was accompanied by a decrease in Bcl-2 levels and an increase in Bax expression in goblet cells.
  
  
  CONCLUSIONS
  In summary, our results suggested that gefinitib may have a potential role in airway remodeling and inflammation, and may be an effective pharmacotherapy for asthma.
authors.affiliation: Department of Pulmonary and Critical Care Medicine, Xijing Hospital, Fourth Military Medical University, Xi' an, China.
authors.forename: Liqiang
authors.initials: L
authors.lastname: Song
authors.forename: Huanzhang
authors.initials: H
authors.lastname: Tang
authors.forename: Dapeng
authors.initials: D
authors.lastname: Liu
authors.forename: Jiao
authors.initials: J
authors.lastname: Song
authors.forename: Yunfu
authors.initials: Y
authors.lastname: Wu
authors.forename: Shuoyao
authors.initials: S
authors.lastname: Qu
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
mesh_terms: D056151:Airway Remodeling / Q000187:drug effects*; D000818:Animals; D001249:Asthma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects; D004804:Eosinophils / Q000166:cytology; D066246:ErbB Receptors / Q000378:metabolism; D000077156:Gefitinib; D007249:Inflammation / Q000276:immunology / Q000517:prevention & control; D007371:Interferon-gamma / Q000032:analysis; D018793:Interleukin-13 / Q000032:analysis; D007958:Leukocyte Count; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D055271:Mucin 5AC / Q000032:analysis; D010047:Ovalbumin / Q000276:immunology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011799:Quinazolines / Q000494:pharmacology* / Q000627:therapeutic use; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D018793:Interleukin-13; C524679:Muc5ac protein, mouse; D055271:Mucin 5AC; D019253:Proto-Oncogene Proteins c-bcl-2; D011799:Quinazolines; D051028:bcl-2-Associated X Protein; D007371:Interferon-gamma; D010047:Ovalbumin; C541485:EGFR protein, mouse; D066246:ErbB Receptors; D000077156:Gefitinib