Oral lovastatin attenuates airway inflammation and mucus secretion in ovalbumin-induced murine model of asthma.
OBJECTIVE
Lovastatin is an effective inhibitor of cholesterol synthesis. A previous study demonstrated that lovastatin can also suppress airway hyperresponsiveness (AHR) in murine model of asthma. We aimed to investigate the effect of lovastatin on mucus secretion and inflammation-associated gene expression in the lungs of murine model of asthma.


METHODS
Female BALB/c mice were sensitized and challenged with ovalbumin (OVA) by intraperitoneal injection, and orally administered lovastatin from days 14 to 27 post-injection. Gene expression in lung tissues was analyzed using real-time polymerase chain reaction. AHR and goblet cell hyperplasia were also examined. BEAS-2B human bronchial epithelial cells were used to evaluate the effect of lovastatin on the expression of cell adhesion molecules, chemokines, and proinflammatory cytokines in vitro.


RESULTS
We showed that lovastatin inhibits the expression of Th2-associated genes, including eotaxins and adhesion molecules, in the lungs of murine model of asthma. Mucin 5AC expression, eosinophil infiltration and goblet cell hyperplasia were significantly decreased in the lung tissue of murine model of asthma treated with lovastatin. Furthermore, lovastatin inhibited AHR and expression of Th2-associated cytokines in bronchoalveolar lavage fluid. However, a high dose (40 mg/kg) of lovastatin was required to decrease specific IgE to OVA levels in serum, and suppress the expression of Th2-associated cytokines in splenocytes. Activated BEAS-2B cells treated with lovastatin exhibited reduced IL-6, eotaxins (CCL11 and CCL24), and intercellular adhesion molecule-1 protein expression. Consistent with this, lovastatin also suppressed the ability of HL-60 cells to adhere to inflammatory BEAS-2B cells.


CONCLUSIONS
These data suggest that lovastatin suppresses mucus secretion and airway inflammation by inhibiting the production of eotaxins and Th2 cytokines in murine model of asthma.
Department of Nursing, Chang Gung University of Science and Technology, Tao-Yuan, Taiwan. ; Research Center for Industry of Human Ecology, Chang Gung University of Science and Technology, Kwei-Shan, Tao-Yuan, Taiwan.
Chian-Jiun
CJ
Liou
Department of Microbiology and Immunology, Graduate Institute of Biomedical Sciences, Chang Gung University, Kwei-Shan, Tao-Yuan, Taiwan.
Pei-Yun
PY
Cheng
Research Center for Industry of Human Ecology, Chang Gung University of Science and Technology, Kwei-Shan, Tao-Yuan, Taiwan. ; Department of Nutrition and Health Sciences, Chang Gung University of Science and Technology, Kwei-Shan, Tao-Yuan, Taiwan. ; Graduate Institute of Health Industry Technology, Chang Gung University of Science and Technology, Kwei-Shan, Tao-Yuan, Taiwan.
Wen-Chung
WC
Huang
Department of Microbiology and Immunology, Graduate Institute of Biomedical Sciences, Chang Gung University, Kwei-Shan, Tao-Yuan, Taiwan.
Cheng-Chi
CC
Chan
Department of Microbiology and Immunology, Graduate Institute of Biomedical Sciences, Chang Gung University, Kwei-Shan, Tao-Yuan, Taiwan.
Meng-Chun
MC
Chen
Department of Microbiology and Immunology, Graduate Institute of Biomedical Sciences, Chang Gung University, Kwei-Shan, Tao-Yuan, Taiwan.
Ming-Ling
ML
Kuo
School of Traditional Chinese Medicine, Chang Gung University, Kwei-Shan, Tao-Yuan, Taiwan. ; Center for Traditional Chinese Medicine, Chang Gung Memorial Hospital at Lin-Kuo, Tao-Yuan, Taiwan.
Jiann-Jong
JJ
Shen
Asthma; MUC5 AC; cytokine; eosinophil; eotaxin; lovastatin