LPS Induces Occludin Dysregulation in Cerebral Microvascular Endothelial Cells via MAPK Signaling and Augmenting MMP-2 Levels
Joint Authors
Qin, Lan-hui
Huang, Wen
Mo, Xue-an
Chen, Yan-lan
Wu, Xiang-hong
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2015, Issue 2015 (31 Dec. 2015), pp.1-9, 9 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2015-07-28
Country of Publication
Egypt
No. of Pages
9
Main Subjects
Abstract EN
Disrupted blood-brain barrier (BBB) integrity contributes to cerebral edema during central nervous system infection.
The current study explored the mechanism of lipopolysaccharide- (LPS-) induced dysregulation of tight junction (TJ) proteins.
Human cerebral microvascular endothelial cells (hCMEC/D3) were exposed to LPS, SB203580 (p38MAPK inhibitor), or SP600125 (JNK inhibitor), and cell vitality was determined by MTT assay.
The proteins expressions of p38MAPK, JNK, and TJs (occludin and zonula occludens- (ZO-) 1) were determined by western blot.
The mRNA levels of TJ components and MMP-2 were measured with quantitative real-time polymerase chain reaction (qRT-PCR), and MMP-2 protein levels were determined by enzyme-linked immunosorbent assay (ELISA).
LPS, SB203580, and SP600125 under respective concentrations of 10, 7.69, or 0.22 µg/mL had no effects on cell vitality.
Treatment with LPS decreased mRNA and protein levels of occludin and ZO-1 and enhanced p38MAPK and JNK phosphorylation and MMP-2 expression.
These effects were attenuated by pretreatment with SB203580 or SP600125, but not in ZO-1 expression.
Both doxycycline hyclate (a total MMP inhibitor) and SB-3CT (a specific MMP-2 inhibitor) partially attenuated the LPS-induced downregulation of occludin.
These data suggest that MMP-2 overexpression and p38MAPK/JNK pathways are involved in the LPS-mediated alterations of occludin in hCMEC/D3; however, ZO-1 levels are not influenced by p38MAPK/JNK.
American Psychological Association (APA)
Qin, Lan-hui& Huang, Wen& Mo, Xue-an& Chen, Yan-lan& Wu, Xiang-hong. 2015. LPS Induces Occludin Dysregulation in Cerebral Microvascular Endothelial Cells via MAPK Signaling and Augmenting MMP-2 Levels. Oxidative Medicine and Cellular Longevity،Vol. 2015, no. 2015, pp.1-9.
https://search.emarefa.net/detail/BIM-1075526
Modern Language Association (MLA)
Qin, Lan-hui…[et al.]. LPS Induces Occludin Dysregulation in Cerebral Microvascular Endothelial Cells via MAPK Signaling and Augmenting MMP-2 Levels. Oxidative Medicine and Cellular Longevity No. 2015 (2015), pp.1-9.
https://search.emarefa.net/detail/BIM-1075526
American Medical Association (AMA)
Qin, Lan-hui& Huang, Wen& Mo, Xue-an& Chen, Yan-lan& Wu, Xiang-hong. LPS Induces Occludin Dysregulation in Cerebral Microvascular Endothelial Cells via MAPK Signaling and Augmenting MMP-2 Levels. Oxidative Medicine and Cellular Longevity. 2015. Vol. 2015, no. 2015, pp.1-9.
https://search.emarefa.net/detail/BIM-1075526
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1075526