title: IκBNS induces Muc5ac expression in epithelial cells and causes airway hyper-responsiveness in murine asthma models.
abstract: BACKGROUND
  In allergic asthma, environmental allergens including house dust mite (HDM) trigger pattern recognition receptors and activate downstream signaling pathways including NF-κB pathways not only in immune cells but also in airway epithelial cells. Recent studies have shown that NF-κB activation is regulated positively or negatively depending on the cellular context by IκBNS (encoded by the gene Nfkbid), one of atypical IκB proteins, in the nucleus. Therefore, we hypothesized that IκBNS expressed in immune cells or epithelial cells is involved in the regulation of asthmatic responses.
  
  
  OBJECTIVE
  To determine the roles of IκBNS in HDM-induced asthmatic responses.
  
  
  METHODS
  Roles of IκBNS in HDM-induced airway inflammation and airway hyper-responsiveness (AHR) were examined by using IκBNS-deficient (Nfkbid-/-) mice. Roles of IκBNS expressed in hematopoietic cells and nonhematopoietic cells were separately evaluated by bone marrow chimeric mice. Roles of IκBNS expressed in murine tracheal epithelial cells (mTECs) were examined by air-liquid interface culture.
  
  
  RESULTS
  House dust mite-induced airway inflammation and AHR were exacerbated in mice lacking IκBNS in hematopoietic cells. In contrast, HDM-induced airway inflammation was exacerbated, but AHR was attenuated in mice lacking IκBNS in nonhematopoietic cells. The induction of Muc5ac, a representative mucin in asthmatic airways, was reduced in Nfkbid-/-mTEC, whereas the induction of Spdef, a master regulator of goblet cell metaplasia, was not impaired in Nfkbid-/-mTEC. Moreover, IκBNS bound to and activated the MUC5AC distal promoter in epithelial cells.
  
  
  CONCLUSIONS
  IκBNS is involved in inducing Muc5ac expression in lung epithelial cells and causing AHR in HDM-induced asthma models.
authors.affiliation: Department of Allergy and Clinical Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Yokota
authors.affiliation: Department of Allergy and Clinical Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Tamachi
authors.affiliation: Department of Allergy and Clinical Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Yokoyama
authors.affiliation: Department of Allergy and Clinical Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Maezawa
authors.affiliation: Department of Allergy and Clinical Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Takatori
authors.affiliation: Department of Allergy and Clinical Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Suto
authors.affiliation: Department of Allergy and Clinical Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Suzuki
authors.affiliation: Department of Allergy and Clinical Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Hirose
authors.affiliation: Laboratory of Immune Regulation, Department of Microbiology and Immunology, Graduate School of Medicine and Laboratory of Mucosal Immunology, WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Takeda
authors.affiliation: Department of Allergy and Clinical Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Nakajima
mesh_terms: D000485:Allergens / Q000276:immunology; D000818:Animals; D001249:Asthma / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D001773:Blood Cells / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D040002:Dermatophagoides pteronyssinus / Q000276:immunology; D004195:Disease Models, Animal; D018450:Disease Progression; D005786:Gene Expression Regulation; D020672:I-kappa B Proteins / Q000235:genetics / Q000378:metabolism*; D018836:Inflammation Mediators / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D055271:Mucin 5AC / Q000235:genetics*; D009093:Mucus / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012130:Respiratory Hypersensitivity / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D020545:Respiratory Mucosa / Q000378:metabolism* / Q000473:pathology
chemical_list: D000485:Allergens; D016207:Cytokines; D020672:I-kappa B Proteins; D018836:Inflammation Mediators; C524679:Muc5ac protein, mouse; D055271:Mucin 5AC
keywords: IκBNS; Muc5ac; airway hyper-responsiveness; asthma