The PPARy agonist, ros,glitazone, attenuates airway inflammation and remodeling via heme oxygenase-1 in murine model of asthma
Aim： Rosiglitazone is one of the specific PPARy agonists showing potential therapeutic effects in asthma. Though PPARy activation was considered protective in inhibiting airway inflammation and remodeling in asthma, the specific mechanisms are still unclear. This study was aimed to investigate wheth...
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| Published in | 中国药理学报：英文版 no. 2; pp. 171 - 178 |
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| Main Author | |
| Format | Journal Article |
| Language | English |
| Published |
2015
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| Subjects | |
| Online Access | Get full text |
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| Summary: | Aim： Rosiglitazone is one of the specific PPARy agonists showing potential therapeutic effects in asthma. Though PPARy activation was considered protective in inhibiting airway inflammation and remodeling in asthma, the specific mechanisms are still unclear. This study was aimed to investigate whether heme oxygenase-1 （HO-1） related pathways were involved in rosiglitazone-activated PPARy signaling in asthma treatment. Methods： Asthma was induced in mice by multiple exposures to ovalbumin （OVA） in 8 weeks. Prior to every OVA challenge, the mice received rosiglitazone （5 mg/kg, po）. After the mice were sacrificed, the bronchoalveolar lavage fluid （BALF）, blood samples and lungs were collected for analyses. The activities of HO-1, MMP-2 and MMP-9 in airway tissue were assessed, and the expression of PPARy, HO-1 and p21 proteins was also examined. Results： Rosiglitazone administration significantly attenuated airway inflammation and remodeling in mice with OVA-induced asthma, which were evidenced by decreased counts of total cells, eosinophils and neutrophils, and decreased levels of IL-5 and IL-13 in BALF, and by decreased airway smooth muscle layer thickness and reduced airway collagen deposition. Furthermore, rosiglitazone administration significantly increased PPARy, HO-1 and p21 expression and HO-1 activity, decreased MMP-2 and MMP-9 activities in airway tissue. All the therapeutic effects of rosiglitazone were significantly impaired by co-administration of the HO-1 inhibitor ZnPP. Conclusion： Rosiglitazone effectively attenuates airway inflammation and remodeling in OVA- induced asthma of mice by activating PPARY/HO-1 signaling pathway. |
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| Bibliography: | asthma; OVA-induced asthma; PPARy; rosiglitazone; HO-1; p21; MMP-2; MMP-9; ZnPP Jing XU, Yan-ting ZHU, Gui-zuo WANG, Dong HAN, Yuan-yuan WU, De-xin ZHANG, Yun LIU, Yong-hong ZHANG, Xin-ming XlE Shao-jun LI, Jia-mei LU, Lu LIU, Wei FENG, Xiu-zhen SUN, Man-xiang LI（ Department of Respiratory Medicine, the Second Affiliated Hospital of Xi＇an Jiaotong University, Xi＇an, Shanxi 710004, China） Aim： Rosiglitazone is one of the specific PPARy agonists showing potential therapeutic effects in asthma. Though PPARy activation was considered protective in inhibiting airway inflammation and remodeling in asthma, the specific mechanisms are still unclear. This study was aimed to investigate whether heme oxygenase-1 （HO-1） related pathways were involved in rosiglitazone-activated PPARy signaling in asthma treatment. Methods： Asthma was induced in mice by multiple exposures to ovalbumin （OVA） in 8 weeks. Prior to every OVA challenge, the mice received rosiglitazone （5 mg/kg, po）. After the mice were sacrificed, the bronchoalveolar lavage fluid （BALF）, blood samples and lungs were collected for analyses. The activities of HO-1, MMP-2 and MMP-9 in airway tissue were assessed, and the expression of PPARy, HO-1 and p21 proteins was also examined. Results： Rosiglitazone administration significantly attenuated airway inflammation and remodeling in mice with OVA-induced asthma, which were evidenced by decreased counts of total cells, eosinophils and neutrophils, and decreased levels of IL-5 and IL-13 in BALF, and by decreased airway smooth muscle layer thickness and reduced airway collagen deposition. Furthermore, rosiglitazone administration significantly increased PPARy, HO-1 and p21 expression and HO-1 activity, decreased MMP-2 and MMP-9 activities in airway tissue. All the therapeutic effects of rosiglitazone were significantly impaired by co-administration of the HO-1 inhibitor ZnPP. Conclusion： Rosiglitazone effectively attenuates airway inflammation and remodeling in OVA- induced asthma of mice by activating PPARY/HO-1 signaling pathway. 31-1347/R |
| ISSN: | 1671-4083 1745-7254 |