title: Airway epithelial NF-κB activation promotes Mycoplasma pneumoniae clearance in mice.
abstract: OBJECTIVE
  Respiratory infections including atypical bacteria Mycoplasma pneumoniae (Mp) contribute to the pathobiology of asthma and chronic obstructive pulmonary disease (COPD). Mp infection mainly targets airway epithelium and activates various signaling pathways such as nuclear factor κB (NF-κB). We have shown that short palate, lung, and nasal epithelium clone 1 (SPLUNC1) serves as a novel host defense protein and is up-regulated upon Mp infection through NF-κB activation in cultured human and mouse primary airway epithelial cells. However, the in vivo role of airway epithelial NF-κB activation in host defense against Mp infection has not been investigated. In the current study, we investigated the effects of in vivo airway epithelial NF-κB activation on lung Mp clearance and its association with airway epithelial SPLUNC1 expression.
  
  
  RESULTS
  Non-antimicrobial tetracycline analog 9-t-butyl doxycycline (9-TB) was initially optimized in mouse primary tracheal epithelial cell culture, and then utilized to induce in vivo airway epithelial specific NF-κB activation in conditional NF-κB transgenic mice (CC10-(CA)IKKβ) with or without Mp infection. Lung Mp load and inflammation were evaluated, and airway epithelial SPLUNC1 protein was examined by immunohistochemistry. We found that 9-TB treatment in NF-κB transgene positive (Tg+), but not transgene negative (Tg-) mice significantly reduced lung Mp load. Moreover, 9-TB increased airway epithelial SPLUNC1 protein expression in NF-κB Tg+ mice.
  
  
  CONCLUSIONS
  By using the non-antimicrobial 9-TB, our study demonstrates that in vivo airway epithelial NF-κB activation promotes lung bacterial clearance, which is accompanied by increased epithelial SPLUNC1 expression.
authors.affiliation: Department of Medicine, National Jewish Health and the University of Colorado Denver, Denver, Colorado, United States of America.
authors.forename: Di
authors.initials: D
authors.lastname: Jiang
authors.forename: Mark L
authors.initials: ML
authors.lastname: Nelson
authors.forename: Fabienne
authors.initials: F
authors.lastname: Gally
authors.forename: Sean
authors.initials: S
authors.lastname: Smith
authors.forename: Qun
authors.initials: Q
authors.lastname: Wu
authors.forename: Maisha
authors.initials: M
authors.lastname: Minor
authors.forename: Stephanie
authors.initials: S
authors.lastname: Case
authors.forename: Jyoti
authors.initials: J
authors.lastname: Thaikoottathil
authors.forename: Hong Wei
authors.initials: HW
authors.lastname: Chu
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004318:Doxycycline / Q000494:pharmacology; D006801:Humans; D007113:Immunity, Innate / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009079:Mucociliary Clearance / Q000187:drug effects / Q000276:immunology; D009177:Mycoplasma pneumoniae / Q000187:drug effects / Q000254:growth & development / Q000276:immunology* / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism* / Q000502:physiology; D011019:Pneumonia, Mycoplasma / Q000276:immunology / Q000378:metabolism / Q000382:microbiology / Q000503:physiopathology*; D020545:Respiratory Mucosa / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology*
chemical_list: D016328:NF-kappa B; D004318:Doxycycline