JNK activation is responsible for mucus overproduction in smoke inhalation injury.
BACKGROUND
Increased mucus secretion is one of the important characteristics of the response to smoke inhalation injuries. We hypothesized that gel-forming mucins may contribute to the increased mucus production in a smoke inhalation injury. We investigated the role of c-Jun N-terminal kinase (JNK) in modulating smoke-induced mucus secretion.


METHODS
We intubated mice and exposed them to smoke from burning cotton for 15 min. Their lungs were then isolated 4 and 24 h after inhalation injury. Three groups of mice were subjected to the smoke inhalation injury: (1) wild-type (WT) mice, (2) mice lacking JNK1 (JNK1-/- mice), and (3) WT mice administered a JNK inhibitor. The JNK inhibitor (SP-600125) was injected into the mice 1 h after injury.


RESULTS
Smoke exposure caused an increase in the production of mucus in the airway epithelium of the mice along with an increase in MUC5AC gene and protein expression, while the expression of MUC5B was not increased compared with control. We found increased MUC5AC protein expression in the airway epithelium of the WT mice groups both 4 and 24 h after smoke inhalation injury. However, overproduction of mucus and increased MUC5AC protein expression induced by smoke inhalation was suppressed in the JNK inhibitor-treated mice and the JNK1 knockout mice. Smoke exposure did not alter the expression of MUC1 and MUC4 proteins in all 3 groups compared with control.


CONCLUSIONS
An increase in epithelial MUC5AC protein expression is associated with the overproduction of mucus in smoke inhalation injury, and that its expression is related on JNK1 signaling.
Pulmonary/Critical Care Unit, Department of Medicine, Massachusettes General Hospital and Harvard Medical School, Boston, MA, USA.
Won-Ii
WI
Choi
Olga
O
Syrkina
Kun Young
KY
Kwon
Deborah A
DA
Quinn
Charles A
CA
Hales
D000818:Animals; D004789:Enzyme Activation; D008168:Lung / Q000378:metabolism*; D048670:MAP Kinase Kinase 4 / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009093:Mucus / Q000378:metabolism*; D015208:Smoke Inhalation Injury / Q000378:metabolism*
D048670:MAP Kinase Kinase 4