Airway epithelial NF-κB activation promotes Mycoplasma pneumoniae clearance in mice

• Published in: PloS one Vol. 7; no. 12; p. e52969
• Main Authors: Jiang, Di, Nelson, Mark L, Gally, Fabienne, Smith, Sean, Wu, Qun, Minor, Maisha, Case, Stephanie, Thaikoottathil, Jyoti, Chu, Hong Wei
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 28-12-2012; Public Library of Science (PLoS)
• Subjects: Activation; Animals; Antibiotics; Antiinfectives and antibacterials; Antimicrobial agents; Asthma; Bacteria; Bacterial infections; Cell culture; Cells, Cultured; Chronic infection; Chronic obstructive pulmonary disease; Doxycycline; Doxycycline - pharmacology; Epithelial cells; Epithelium; Humans; Immunity, Innate - physiology; Immunohistochemistry; In vivo methods and tests; Infections; Inflammation; Lung diseases; Medicine; Mice; Mice, Inbred C57BL; Mice, Transgenic; Mucociliary Clearance - drug effects; Mucociliary Clearance - immunology; Mycoplasma pneumoniae; Mycoplasma pneumoniae - drug effects; Mycoplasma pneumoniae - growth & development; Mycoplasma pneumoniae - immunology; Mycoplasma pneumoniae - metabolism; NF-kappa B - metabolism; NF-kappa B - physiology; NF-κB protein; Obstructive lung disease; Palate; Pneumonia, Mycoplasma - immunology; Pneumonia, Mycoplasma - metabolism; Pneumonia, Mycoplasma - microbiology; Pneumonia, Mycoplasma - physiopathology; Respiratory Mucosa - drug effects; Respiratory Mucosa - immunology; Respiratory Mucosa - metabolism; Respiratory Mucosa - physiopathology; Respiratory tract; Rodents; Signaling; Transgenic animals; Transgenic mice; United States > US; Colorado
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0052969

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.
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.
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.