Dexamethasone Suppressed LPS-Induced Matrix Metalloproteinase and Its Effect on Endothelial Glycocalyx Shedding
The aim of this study is to determine the mechanism of sepsis-induced vascular hyperpermeability and the beneficial effect of glucocorticoid in protecting vascular endothelium. Male Sprague-Dawley rats were given either a bolus intraperitoneal injection of a nonlethal dose of LPS (Escherichia coli 0...
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| Format: | Article |
| Language: | English |
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Wiley
2015-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2015/912726 |
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| author | Na Cui Hao Wang Yun Long Longxiang Su Dawei Liu |
| author_facet | Na Cui Hao Wang Yun Long Longxiang Su Dawei Liu |
| author_sort | Na Cui |
| collection | DOAJ |
| description | The aim of this study is to determine the mechanism of sepsis-induced vascular hyperpermeability and the beneficial effect of glucocorticoid in protecting vascular endothelium. Male Sprague-Dawley rats were given either a bolus intraperitoneal injection of a nonlethal dose of LPS (Escherichia coli 055:B5, 10 mg/kg, Sigma) or vehicle (pyrogen-free water). Animals of treatment groups were also given either dexamethasone (4 mg/kg, 30 min prior to LPS injection) or the matrix metalloproteinases (MMPs) inhibitor doxycycline (4 mg/kg, 30 min after LPS injection). Both activities and protein levels of MMP-2 p<0.001 and MMP-9 p<0.001 were significantly upregulated in aortic homogenates from LPS-treated rats, associated with decreased ZO-1 p<0.001 and syndecan-1 p=0.011 protein contents. Both dexamethasone and doxycycline could significantly inhibit MMPs activity and reserve the expressions of ZO-1 and syndecan-1. The inhibition of MMPs by dexamethasone was significantly lower than that by doxycycline, while the rescue of syndecan-1 expression from LPS-induced endotoxemic rat thoracic aorta was significantly higher in the dexamethasone-treated compared to the doxycycline-treated p=0.03. In conclusion, activation of MMPs plays important role in regulating ZO-1 and syndecan-1 protein levels in LPS mediated endothelial perturbation. Both dexamethasone and doxycycline inhibit activation of MMPs that may contribute to the rescue of ZO-1 and syndecan-1 expression. |
| format | Article |
| id | doaj-art-ee43cc60abed4bd88347118e5ff1d940 |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2015-01-01 |
| publisher | Wiley |
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| series | Mediators of Inflammation |
| spelling | doaj-art-ee43cc60abed4bd88347118e5ff1d9402025-02-03T01:03:08ZengWileyMediators of Inflammation0962-93511466-18612015-01-01201510.1155/2015/912726912726Dexamethasone Suppressed LPS-Induced Matrix Metalloproteinase and Its Effect on Endothelial Glycocalyx SheddingNa Cui0Hao Wang1Yun Long2Longxiang Su3Dawei Liu4Department of Critical Care Medicine, Peking Union Medical College Hospital, Beijing 100730, ChinaDepartment of Critical Care Medicine, Peking Union Medical College Hospital, Beijing 100730, ChinaDepartment of Critical Care Medicine, Peking Union Medical College Hospital, Beijing 100730, ChinaDepartment of Critical Care Medicine, Peking Union Medical College Hospital, Beijing 100730, ChinaDepartment of Critical Care Medicine, Peking Union Medical College Hospital, Beijing 100730, ChinaThe aim of this study is to determine the mechanism of sepsis-induced vascular hyperpermeability and the beneficial effect of glucocorticoid in protecting vascular endothelium. Male Sprague-Dawley rats were given either a bolus intraperitoneal injection of a nonlethal dose of LPS (Escherichia coli 055:B5, 10 mg/kg, Sigma) or vehicle (pyrogen-free water). Animals of treatment groups were also given either dexamethasone (4 mg/kg, 30 min prior to LPS injection) or the matrix metalloproteinases (MMPs) inhibitor doxycycline (4 mg/kg, 30 min after LPS injection). Both activities and protein levels of MMP-2 p<0.001 and MMP-9 p<0.001 were significantly upregulated in aortic homogenates from LPS-treated rats, associated with decreased ZO-1 p<0.001 and syndecan-1 p=0.011 protein contents. Both dexamethasone and doxycycline could significantly inhibit MMPs activity and reserve the expressions of ZO-1 and syndecan-1. The inhibition of MMPs by dexamethasone was significantly lower than that by doxycycline, while the rescue of syndecan-1 expression from LPS-induced endotoxemic rat thoracic aorta was significantly higher in the dexamethasone-treated compared to the doxycycline-treated p=0.03. In conclusion, activation of MMPs plays important role in regulating ZO-1 and syndecan-1 protein levels in LPS mediated endothelial perturbation. Both dexamethasone and doxycycline inhibit activation of MMPs that may contribute to the rescue of ZO-1 and syndecan-1 expression.http://dx.doi.org/10.1155/2015/912726 |
| spellingShingle | Na Cui Hao Wang Yun Long Longxiang Su Dawei Liu Dexamethasone Suppressed LPS-Induced Matrix Metalloproteinase and Its Effect on Endothelial Glycocalyx Shedding Mediators of Inflammation |
| title | Dexamethasone Suppressed LPS-Induced Matrix Metalloproteinase and Its Effect on Endothelial Glycocalyx Shedding |
| title_full | Dexamethasone Suppressed LPS-Induced Matrix Metalloproteinase and Its Effect on Endothelial Glycocalyx Shedding |
| title_fullStr | Dexamethasone Suppressed LPS-Induced Matrix Metalloproteinase and Its Effect on Endothelial Glycocalyx Shedding |
| title_full_unstemmed | Dexamethasone Suppressed LPS-Induced Matrix Metalloproteinase and Its Effect on Endothelial Glycocalyx Shedding |
| title_short | Dexamethasone Suppressed LPS-Induced Matrix Metalloproteinase and Its Effect on Endothelial Glycocalyx Shedding |
| title_sort | dexamethasone suppressed lps induced matrix metalloproteinase and its effect on endothelial glycocalyx shedding |
| url | http://dx.doi.org/10.1155/2015/912726 |
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