Inhibition of JNK activation prolongs survival after smoke inhalation from fires.
Initial injury from smoke inhalation is mainly to the trachea and bronchi and is characterized by mucosal hyperemia and increased microvascular permeability, exfoliation of epithelial lining, mucous secretion, mucous plugging, and an acute inflammatory cell influx. In this study, we explore the role of the c-Jun N-terminal protein kinase (JNK) pathway in smoke inhalation lung injury using a rat model of exposure to smoke from burning cotton. Male Sprague-Dawley rats were exposed to smoke from burning cotton for 15 min, and 1 h after injury a JNK inhibitor (SP-600125) or vehicle was injected. We measured neutrophil influx, cytokine release, percent of apoptotic cells, airway plugging, and survival. Administration of a JNK inhibitor 1 h after smoke inhalation decreased airway apoptosis, mucous plugging, influx of inflammatory cells, and the release of cytokines and significantly prolonged animal survival (P < 0.05). These in vivo data show that the JNK pathway plays a critical role in smoke-induced lung injury and offer an attractive therapeutic approach for this injury.
Syrkina
Olga L
OL
Pulmonary and Critical Care Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA. osyrkina@partners.org
Quinn
Deborah A
DA
Jung
Walter
W
Ouyang
Bin
B
Hales
Charles A
CA
D000818:Animals; D000873:Anthracenes / Q000627:therapeutic use*; D017209:Apoptosis / Q000502:physiology; D004121:Dimethyl Sulfoxide / Q000627:therapeutic use; D004789:Enzyme Activation / Q000187:drug effects*; D004847:Epithelial Cells / Q000201:enzymology; D020287:In Situ Nick-End Labeling; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D051381:Rats; D012137:Respiratory System / Q000166:cytology / Q000201:enzymology; D015208:Smoke Inhalation Injury / Q000188:drug therapy* / Q000473:pathology
D000873:Anthracenes; C432165:pyrazolanthrone; D011065:Poly(ADP-ribose) Polymerases; D048031:JNK Mitogen-Activated Protein Kinases; D004121:Dimethyl Sulfoxide