Presence of secretory cellular apoptosis susceptibility protein in cerebrospinal fluids of patients with intracerebral hemorrhage caused by stroke and neurotrauma.
OBJECTIVE
The blood-brain barrier (BBB) is a specialized structure that separates blood vessels from the central nervous system (CNS) and restricts the entry of biomolecules and cells into the brain. Matrix metalloproteinase-2 (MMP-2) produced by interferon-gamma-activated microglia (brain macrophages) is essential for disrupting the glia limitans of BBB, which is critical for lymphocytes penetration into brain capillaries in various CNS disorders. The cellular apoptosis susceptibility (CSE1L/CAS) protein has been shown to regulate MMP-2 secretion.


METHODS
We examined if CSE1L played a role in regulating the progression of intracerebral brain hemorrhage disorders.


RESULTS
CSE1L was detected by immunoblotting in cerebrospinal fluids (CSFs) of patients with intracerebral hemorrhage brain disorders, including stroke and neurotrauma. Interferon-gamma treatment induced CSE1L expression and increased the secretions of CSE1L and MMP-2 by U937 macrophages. Moreover, tranfection of U937 macrophages with siRNA that targeted CSE1L inhibited interferon-gamma-induced CSE1L and MMP-2 secretion by U937 macrophages. The numbers of lymphocytes in CSF were correlated with the levels of CSE1L and MMP-2 in patients' CSF.


CONCLUSIONS
Our results suggest that CSE1L plays a role in regulating MMP-2-mediated BBB breakdown and it may be a target for control of BBB permeability in intracerebral brain hemorrhage disorders.
Tung
Jai-Nien
JN
Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan, Taiwan.
Tsao
Tang-Yi
TY
Chen
Shun-Liang
SL
Tai
Cheng-Jeng
CJ
Shen
Shing-Chuan
SC
Cheng
Ya-Wen
YW
Jiang
Ming-Chung
MC
D000368:Aged; D000369:Aged, 80 and over; D001812:Blood-Brain Barrier / Q000502:physiology; D001930:Brain Injuries / Q000134:cerebrospinal fluid* / Q000150:complications; D045744:Cell Line, Tumor; D029563:Cellular Apoptosis Susceptibility Protein / Q000134:cerebrospinal fluid* / Q000235:genetics; D002543:Cerebral Hemorrhage / Q000134:cerebrospinal fluid* / Q000150:complications; D006801:Humans; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D008875:Middle Aged; D034741:RNA, Small Interfering / Q000235:genetics; D020521:Stroke / Q000134:cerebrospinal fluid* / Q000150:complications; D014162:Transfection / Q000379:methods; D020298:U937 Cells
D029563:Cellular Apoptosis Susceptibility Protein; D034741:RNA, Small Interfering; D007371:Interferon-gamma; D020778:Matrix Metalloproteinase 2