title: Cigarette smoke exacerbates mouse allergic asthma through Smad proteins expressed in mast cells.
abstract: BACKGROUND
  Many studies have found that smoking reduces lung function, but the relationship between cigarette smoke and allergic asthma has not been clearly elucidated, particularly the role of mast cells. This study aimed to investigate the effects of smoke exposure on allergic asthma and its association with mast cells.
  
  
  METHODS
  BALB/c mice were sensitized and challenged by OVA to induce asthma, and bone marrow-derived mast cells (BMMCs) were stimulated with antigen/antibody reaction. Mice or BMMCs were exposed to cigarette smoke or CSE solution for 1 mo or 6 h, respectively. The recruitment of inflammatory cells into BAL fluid or lung tissues was determined by Diff-Quik or H&E staining, collagen deposition by Sircol assay, penh values by a whole-body plethysmography, co-localization of tryptase and Smad3 by immunohistochemistry, IgE and TGF-β level by ELISA, expressions of Smads proteins, activities of signaling molecules, or TGF-β mRNA by immunoblotting and RT-PCR.
  
  
  RESULTS
  Cigarette smoke enhanced OVA-specific IgE levels, penh values, recruitment of inflammatory cells including mast cells, expressions of smad family, TGF-β mRNA and proteins, and cytokines, phosphorylations of Smad2 and 3, and MAP kinases, co-localization of tryptase and Smad3, and collagen deposition more than those of BAL cells and lung tissues of OVA-induced allergic mice. CSE solution pretreatment enhanced expressions of TGF-β, Smad3, activities of MAP kinases, NF-κB/AP-1 or PAI-1 more than those of activated-BMMCs.
  
  
  CONCLUSIONS
  The data suggest that smoke exposure enhances antigen-induced mast cell activation via TGF-β/Smad signaling pathways in mouse allergic asthma, and that it exacerbates airway inflammation and remodeling.
authors.affiliation: Department of Pharmacology and Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon 440-726, Korea.
authors.forename: Dae Yong
authors.initials: DY
authors.lastname: Kim
authors.forename: Eun Young
authors.initials: EY
authors.lastname: Kwon
authors.forename: Gwan Ui
authors.initials: GU
authors.lastname: Hong
authors.forename: Yun Song
authors.initials: YS
authors.lastname: Lee
authors.forename: Seung-Hyo
authors.initials: SH
authors.lastname: Lee
authors.forename: Jai Youl
authors.initials: JY
authors.lastname: Ro
mesh_terms: D000818:Animals; D000937:Antigen-Antibody Reactions; D001249:Asthma / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D015153:Blotting, Western; D016535:Bronchial Hyperreactivity / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D001985:Bronchial Provocation Tests; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D016084:Bronchoconstriction; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007073:Immunoglobulin E / Q000378:metabolism; D007150:Immunohistochemistry; D008168:Lung / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D008407:Mast Cells / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010047:Ovalbumin; D010766:Phosphorylation; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D010993:Plethysmography, Whole Body; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D051785:Smad Proteins / Q000235:genetics / Q000378:metabolism*; D051899:Smad2 Protein / Q000378:metabolism; D051900:Smad3 Protein / Q000378:metabolism; D012907:Smoking / Q000276:immunology*; D013997:Time Factors; D018808:Transcription Factor AP-1 / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism; D053802:Tryptases / Q000378:metabolism
chemical_list: D016207:Cytokines; D016328:NF-kappa B; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D051785:Smad Proteins; D051899:Smad2 Protein; C497783:Smad2 protein, mouse; D051900:Smad3 Protein; C497791:Smad3 protein, mouse; D018808:Transcription Factor AP-1; D016212:Transforming Growth Factor beta; D007073:Immunoglobulin E; D010047:Ovalbumin; D003094:Collagen; D020928:Mitogen-Activated Protein Kinases; D053802:Tryptases