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Dexamethasone Suppressed LPS-Induced Matrix Metalloproteinase and Its Effect on Endothelial Glycocalyx Shedding.

Cui N, Wang H, Long Y, Su L, Liu D - Mediators Inflamm. (2015)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Critical Care Medicine, Peking Union Medical College Hospital, Beijing 100730, China.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus

Immunoblotting of ZO-1. Proteins of aortic tissues were extracted from each of the indicated groups and immunoblotted for ZO-1 as described in the method. (a) One representative image data of immunoblotting. GAPDH was used as loading control. Each group was loaded in triplicate. (b) Densitometric analysis data of the relative expression of ZO-1 (mean ± SD, n = 8). ∗p < 0.05; ∗∗p < 0.001.
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fig4: Immunoblotting of ZO-1. Proteins of aortic tissues were extracted from each of the indicated groups and immunoblotted for ZO-1 as described in the method. (a) One representative image data of immunoblotting. GAPDH was used as loading control. Each group was loaded in triplicate. (b) Densitometric analysis data of the relative expression of ZO-1 (mean ± SD, n = 8). ∗p < 0.05; ∗∗p < 0.001.

Mentions: Protein levels of ZO-1 in the aortic tissue from each treatment group were examined by immunoblotting. As shown in Figure 4, under “Control” condition or in the presence of dexamethasone alone, ZO-1 was easily detectable in aortic tissue homogenate by immunoblotting assay. When the animals were given LPS, however, ZO-1 expression in the aortic tissue was remarkably decreased (Figures 4(a) and 4(b), p < 0.001). Doxycycline could significantly block LPS-induced decline of ZO-1 expression (p = 0.006), and, similarly, dexamethasone could also dramatically reduce LPS-induced decline of ZO-1 expression (p < 0.05). Although the effect of dexamethasone on ZO-1 restoration in the presence of LPS was less potent than that of doxycycline, there was no statistical difference between these two reagents.


Dexamethasone Suppressed LPS-Induced Matrix Metalloproteinase and Its Effect on Endothelial Glycocalyx Shedding.

Cui N, Wang H, Long Y, Su L, Liu D - Mediators Inflamm. (2015)

Immunoblotting of ZO-1. Proteins of aortic tissues were extracted from each of the indicated groups and immunoblotted for ZO-1 as described in the method. (a) One representative image data of immunoblotting. GAPDH was used as loading control. Each group was loaded in triplicate. (b) Densitometric analysis data of the relative expression of ZO-1 (mean ± SD, n = 8). ∗p < 0.05; ∗∗p < 0.001.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4493300&req=5

fig4: Immunoblotting of ZO-1. Proteins of aortic tissues were extracted from each of the indicated groups and immunoblotted for ZO-1 as described in the method. (a) One representative image data of immunoblotting. GAPDH was used as loading control. Each group was loaded in triplicate. (b) Densitometric analysis data of the relative expression of ZO-1 (mean ± SD, n = 8). ∗p < 0.05; ∗∗p < 0.001.
Mentions: Protein levels of ZO-1 in the aortic tissue from each treatment group were examined by immunoblotting. As shown in Figure 4, under “Control” condition or in the presence of dexamethasone alone, ZO-1 was easily detectable in aortic tissue homogenate by immunoblotting assay. When the animals were given LPS, however, ZO-1 expression in the aortic tissue was remarkably decreased (Figures 4(a) and 4(b), p < 0.001). Doxycycline could significantly block LPS-induced decline of ZO-1 expression (p = 0.006), and, similarly, dexamethasone could also dramatically reduce LPS-induced decline of ZO-1 expression (p < 0.05). Although the effect of dexamethasone on ZO-1 restoration in the presence of LPS was less potent than that of doxycycline, there was no statistical difference between these two reagents.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Critical Care Medicine, Peking Union Medical College Hospital, Beijing 100730, China.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus