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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

Quantification of syndecan-1 in aortic homogenates by ELISA (mean ± SD, n = 8). ∗p < 0.05; ∗∗p < 0.001.
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fig5: Quantification of syndecan-1 in aortic homogenates by ELISA (mean ± SD, n = 8). ∗p < 0.05; ∗∗p < 0.001.

Mentions: In order to further examine the effect of LPS and dexamethasone or doxycycline on endothelial glycocalyx shedding, level of syndecan-1 in the aortic tissue was quantified using a commercially available ELISA assay. As shown in Figure 5, fair amount of syndecan-1 (>4.8 ng/mL) was found in the “Control” condition or in the presence of dexamethasone alone. Consistent with the result of ZO-1 expression, syndecan-1 was significantly suppressed by LPS (2.43 ± 1.56 ng/mL versus 4.93 ± 1.85 ng/mL of Control, p < 0.01). Again, both doxycycline and dexamethasone were able to partially but significantly block LPS-induced decline of syndecan-1 expression in the aortic tissues (p < 0.05).


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)

Quantification of syndecan-1 in aortic homogenates by ELISA (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

fig5: Quantification of syndecan-1 in aortic homogenates by ELISA (mean ± SD, n = 8). ∗p < 0.05; ∗∗p < 0.001.
Mentions: In order to further examine the effect of LPS and dexamethasone or doxycycline on endothelial glycocalyx shedding, level of syndecan-1 in the aortic tissue was quantified using a commercially available ELISA assay. As shown in Figure 5, fair amount of syndecan-1 (>4.8 ng/mL) was found in the “Control” condition or in the presence of dexamethasone alone. Consistent with the result of ZO-1 expression, syndecan-1 was significantly suppressed by LPS (2.43 ± 1.56 ng/mL versus 4.93 ± 1.85 ng/mL of Control, p < 0.01). Again, both doxycycline and dexamethasone were able to partially but significantly block LPS-induced decline of syndecan-1 expression in the aortic tissues (p < 0.05).

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