Abstract
Obese patients with asthma respond poorly to conventional asthma medications, resulting in severe symptoms and poor prognosis. Roflumilast, a phosphodiesterase-4 inhibitor that lowers the levels of various substances that are implicated in obese subjects with asthma, may be effective in the treatment of those subjects. We evaluated the potential of roflumilast as a novel therapeutic agent for obese subjects with asthma. We designed three models: diet-induced obesity (DIO); DIO with ovalbumin (OVA); and OVA. We fed C57BL/6J mice a high-fat diet for 3 months with or without OVA sensitization and challenge. Roflumilast or dexamethasone was administered orally three times at 2-day intervals in the last experimental week. Airway hyperresponsiveness resulting from DIO significantly improved in the roflumilast-treated group compared with the dexamethasonetreated groups. Although DIO did not affect the cell proliferation in bronchoalveolar lavage fluid, increased fibrosis was seen in the DIO group, which significantly improved from treatment with roflumilast. DIO-induced changes in adiponectin and leptin levels were improved by roflumilast, whereas dexamethasone aggravated them. mRNA levels and proteins of TNF-a, transforming growth factor-b, IL-1b, and IFN-g increased in the DIO group and decreased with roflumilast. The reactive oxygen species levels were also increased in the DIO group and decreased by roflumilast. In the DIO plus OVA and OVA models, roflumilast improved Th1 and Th2 cell activation to a greater extent than dexamethasone. Roflumilast is significantly more effective than dexamethasone against airway hyperresponsiveness caused by DIO in the murine model. Roflumilast may represent a promising therapeutic agent for the treatment of obese patients with asthma.
| Original language | English |
|---|---|
| Pages (from-to) | 82-91 |
| Number of pages | 10 |
| Journal | American Journal of Respiratory Cell and Molecular Biology |
| Volume | 55 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 2016 Jul 1 |
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All Science Journal Classification (ASJC) codes
- Molecular Biology
- Pulmonary and Respiratory Medicine
- Clinical Biochemistry
- Cell Biology
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Roflumilast ameliorates airway hyperresponsiveness caused by diet-induced obesity in a murine model. / Park, Hye Jung; Lee, Jae Hyun; Park, Yoon Hee; Han, Heejae; Sim, Da Woon; Park, Kyung Hee; Park, Jungwon.
In: American Journal of Respiratory Cell and Molecular Biology, Vol. 55, No. 1, 01.07.2016, p. 82-91.Research output: Contribution to journal › Article
TY - JOUR
T1 - Roflumilast ameliorates airway hyperresponsiveness caused by diet-induced obesity in a murine model
AU - Park, Hye Jung
AU - Lee, Jae Hyun
AU - Park, Yoon Hee
AU - Han, Heejae
AU - Sim, Da Woon
AU - Park, Kyung Hee
AU - Park, Jungwon
PY - 2016/7/1
Y1 - 2016/7/1
N2 - Obese patients with asthma respond poorly to conventional asthma medications, resulting in severe symptoms and poor prognosis. Roflumilast, a phosphodiesterase-4 inhibitor that lowers the levels of various substances that are implicated in obese subjects with asthma, may be effective in the treatment of those subjects. We evaluated the potential of roflumilast as a novel therapeutic agent for obese subjects with asthma. We designed three models: diet-induced obesity (DIO); DIO with ovalbumin (OVA); and OVA. We fed C57BL/6J mice a high-fat diet for 3 months with or without OVA sensitization and challenge. Roflumilast or dexamethasone was administered orally three times at 2-day intervals in the last experimental week. Airway hyperresponsiveness resulting from DIO significantly improved in the roflumilast-treated group compared with the dexamethasonetreated groups. Although DIO did not affect the cell proliferation in bronchoalveolar lavage fluid, increased fibrosis was seen in the DIO group, which significantly improved from treatment with roflumilast. DIO-induced changes in adiponectin and leptin levels were improved by roflumilast, whereas dexamethasone aggravated them. mRNA levels and proteins of TNF-a, transforming growth factor-b, IL-1b, and IFN-g increased in the DIO group and decreased with roflumilast. The reactive oxygen species levels were also increased in the DIO group and decreased by roflumilast. In the DIO plus OVA and OVA models, roflumilast improved Th1 and Th2 cell activation to a greater extent than dexamethasone. Roflumilast is significantly more effective than dexamethasone against airway hyperresponsiveness caused by DIO in the murine model. Roflumilast may represent a promising therapeutic agent for the treatment of obese patients with asthma.
AB - Obese patients with asthma respond poorly to conventional asthma medications, resulting in severe symptoms and poor prognosis. Roflumilast, a phosphodiesterase-4 inhibitor that lowers the levels of various substances that are implicated in obese subjects with asthma, may be effective in the treatment of those subjects. We evaluated the potential of roflumilast as a novel therapeutic agent for obese subjects with asthma. We designed three models: diet-induced obesity (DIO); DIO with ovalbumin (OVA); and OVA. We fed C57BL/6J mice a high-fat diet for 3 months with or without OVA sensitization and challenge. Roflumilast or dexamethasone was administered orally three times at 2-day intervals in the last experimental week. Airway hyperresponsiveness resulting from DIO significantly improved in the roflumilast-treated group compared with the dexamethasonetreated groups. Although DIO did not affect the cell proliferation in bronchoalveolar lavage fluid, increased fibrosis was seen in the DIO group, which significantly improved from treatment with roflumilast. DIO-induced changes in adiponectin and leptin levels were improved by roflumilast, whereas dexamethasone aggravated them. mRNA levels and proteins of TNF-a, transforming growth factor-b, IL-1b, and IFN-g increased in the DIO group and decreased with roflumilast. The reactive oxygen species levels were also increased in the DIO group and decreased by roflumilast. In the DIO plus OVA and OVA models, roflumilast improved Th1 and Th2 cell activation to a greater extent than dexamethasone. Roflumilast is significantly more effective than dexamethasone against airway hyperresponsiveness caused by DIO in the murine model. Roflumilast may represent a promising therapeutic agent for the treatment of obese patients with asthma.
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UR - http://www.scopus.com/inward/citedby.url?scp=84988924403&partnerID=8YFLogxK
U2 - 10.1165/rcmb.2015-0345OC
DO - 10.1165/rcmb.2015-0345OC
M3 - Article
C2 - 26756251
AN - SCOPUS:84988924403
VL - 55
SP - 82
EP - 91
JO - American Journal of Respiratory Cell and Molecular Biology
JF - American Journal of Respiratory Cell and Molecular Biology
SN - 1044-1549
IS - 1
ER -