title: Differential expression and function of breast regression protein 39 (BRP-39) in murine models of subacute cigarette smoke exposure and allergic airway inflammation.
abstract: BACKGROUND
  While the presence of the chitinase-like molecule YKL40 has been reported in COPD and asthma, its relevance to inflammatory processes elicited by cigarette smoke and common environmental allergens, such as house dust mite (HDM), is not well understood. The objective of the current study was to assess expression and function of BRP-39, the murine equivalent of YKL40 in a murine model of cigarette smoke-induced inflammation and contrast expression and function to a model of HDM-induced allergic airway inflammation.
  
  
  METHODS
  CD1, C57BL/6, and BALB/c mice were room air- or cigarette smoke-exposed for 4 days in a whole-body exposure system. In separate experiments, BALB/c mice were challenged with HDM extract once a day for 10 days. BRP-39 was assessed by ELISA and immunohistochemistry. IL-13, IL-1R1, IL-18, and BRP-39 knock out (KO) mice were utilized to assess the mechanism and relevance of BRP-39 in cigarette smoke- and HDM-induced airway inflammation.
  
  
  RESULTS
  Cigarette smoke exposure elicited a robust induction of BRP-39 but not the catalytically active chitinase, AMCase, in lung epithelial cells and alveolar macrophages of all mouse strains tested. Both BRP-39 and AMCase were increased in lung tissue after HDM exposure. Examining smoke-exposed IL-1R1, IL-18, and IL-13 deficient mice, BRP-39 induction was found to be IL-1 and not IL-18 or IL-13 dependent, while induction of BRP-39 by HDM was independent of IL-1 and IL-13. Despite the importance of BRP-39 in cellular inflammation in HDM-induced airway inflammation, BRP-39 was found to be redundant for cigarette smoke-induced airway inflammation and the adjuvant properties of cigarette smoke.
  
  
  CONCLUSIONS
  These data highlight the contrast between the importance of BRP-39 in HDM- and cigarette smoke-induced inflammation. While functionally important in HDM-induced inflammation, BRP-39 is a biomarker of cigarette smoke induced inflammation which is the byproduct of an IL-1 inflammatory pathway.
authors.affiliation: 1Medical Sciences Graduate Program, McMaster University, Hamilton, ON,Canada.
authors.forename: Jake K
authors.initials: JK
authors.lastname: Nikota
authors.forename: Fernando M
authors.initials: FM
authors.lastname: Botelho
authors.forename: Carla Mt
authors.initials: CM
authors.lastname: Bauer
authors.forename: Manel
authors.initials: M
authors.lastname: Jordana
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Coyle
authors.forename: Alison A
authors.initials: AA
authors.lastname: Humbles
authors.forename: Martin R
authors.initials: MR
authors.lastname: Stampfli
mesh_terms: D000818:Animals; D039741:Antigens, Dermatophagoides; D000071451:Chitinase-3-Like Protein 1; D002688:Chitinases / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006023:Glycoproteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D018836:Inflammation Mediators / Q000378:metabolism; D008168:Lung / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010047:Ovalbumin; D011014:Pneumonia / Q000209:etiology / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D012907:Smoking / Q000009:adverse effects*; D013997:Time Factors
chemical_list: D039741:Antigens, Dermatophagoides; C509289:Chil1 protein, mouse; D000071451:Chitinase-3-Like Protein 1; D016207:Cytokines; D006023:Glycoproteins; D018836:Inflammation Mediators; D010047:Ovalbumin; C499255:AMCase, mouse; D002688:Chitinases