title: Periostin is required for maximal airways inflammation and hyperresponsiveness in mice.
abstract: BACKGROUND
  Periostin, a secreted extracellular matrix protein, has been localized to deposits of subepithelial fibrosis in asthmatic patients, and periostin levels have been linked to increases in IL-13.
  
  
  OBJECTIVE
  We hypothesized that periostin is required for airway inflammatory responses to a physiologic aeroallergen, house dust mite (HDM).
  
  
  METHODS
  We studied F4-F6 B6;129-Postn(tm1Jmol)/J wild-type (Postn(+/+)) and null (Postn(-/-)) mice, as well as C57BL/6 mice treated with either IgM or OC-20 periostin neutralizing antibody. Mice were exposed to 5 doses of HDM intranasally over a 16-day period.
  
  
  RESULTS
  HDM increased airways responsiveness in Postn(+/+) but not Postn(-/-) mice. In addition, HDM-treated C57BL/6 mice injected with OC-20 had lower airways responsiveness than HDM-treated mice injected with IgM. Compared with Postn(+/+) mice, Postn(-/-) mice showed decreases in HDM-induced inflammation and mucous metaplasia, as well as reduced IL-4, IL-25, CD68, Gob5, and periostin mRNA expression. OC-20 antibody produced similar results. HDM exposure increased periostin expression in the airway epithelium, subepithelium, smooth muscle and inflammatory cells. OC-20 blocked the HDM-induced IgE response, and T cells incubated with dendritic cells (DCs) from Postn(-/-) mice or treated with OC-20 showed deficient DNA synthesis and IL-13 responses compared with T cells incubated with wild-type DCs. Finally, adoptive transfer of bone marrow-derived DCs from Postn(+/+) mice was sufficient to promote allergic responses in F6 Postn(-/-) littermates.
  
  
  CONCLUSIONS
  In mice, periostin is required for maximal airways hyperresponsiveness and inflammation after HDM sensitization and challenge. Periostin is required for maximal HDM-induced T-cell responses.
authors.affiliation: Department of Pediatrics and Communicable Diseases, University of Michigan Medical School, Ann Arbor, Mich.
authors.forename: J Kelley
authors.initials: JK
authors.lastname: Bentley
authors.affiliation: Department of Pediatrics and Communicable Diseases, University of Michigan Medical School, Ann Arbor, Mich.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, Mich.
authors.forename: Jun Young
authors.initials: JY
authors.lastname: Hong
authors.affiliation: Department of Pediatrics and Communicable Diseases, University of Michigan Medical School, Ann Arbor, Mich.
authors.forename: Antonia P
authors.initials: AP
authors.lastname: Popova
authors.affiliation: Department of Pediatrics and Communicable Diseases, University of Michigan Medical School, Ann Arbor, Mich.
authors.forename: Jing
authors.initials: J
authors.lastname: Lei
authors.affiliation: Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Mich.
authors.forename: Bethany B
authors.initials: BB
authors.lastname: Moore
authors.affiliation: Department of Pediatrics and Communicable Diseases, University of Michigan Medical School, Ann Arbor, Mich; Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, Mich. Electronic address: mhershen@umich.edu.
authors.forename: Marc B
authors.initials: MB
authors.lastname: Hershenson
mesh_terms: D000485:Allergens / Q000276:immunology; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000276:immunology*; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000276:immunology*; D045424:Complex Mixtures / Q000494:pharmacology; D003713:Dendritic Cells / Q000276:immunology; D040002:Dermatophagoides pteronyssinus / Q000276:immunology; D007073:Immunoglobulin E / Q000097:blood; D008168:Lung / Q000276:immunology; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010047:Ovalbumin / Q000276:immunology; D011014:Pneumonia / Q000276:immunology*; D012333:RNA, Messenger / Q000378:metabolism; D012130:Respiratory Hypersensitivity / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000485:Allergens; D015815:Cell Adhesion Molecules; D045424:Complex Mixtures; C082838:Postn protein, mouse; D012333:RNA, Messenger; D007073:Immunoglobulin E; D010047:Ovalbumin
keywords: CD11b; Periostin; asthma; house dust mite; inflammation; integrin; matricellular protein; mouse models