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Expression of plasminogen activator inhibitor‐1 and protease nexin‐1 in human astrocytes: Response to injury‐related factors
Author(s) -
Hultman Karin,
Blomstrand Fredrik,
Nilsson Michael,
Wilhelmsson Ulrika,
Malmgren Kristina,
Pekny Milos,
Kousted Tina,
Jern Christina,
TjärnlundWolf Anna
Publication year - 2010
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.22412
Subject(s) - serpin , plasminogen activator inhibitor 1 , serine protease , astrocyte , plasminogen activator , biology , tissue plasminogen activator , hypoxia (environmental) , glial fibrillary acidic protein , tumor necrosis factor alpha , endocrinology , protease , immunology , central nervous system , immunohistochemistry , chemistry , biochemistry , gene , enzyme , organic chemistry , oxygen
Astrocytes play a diverse role in central nervous system (CNS) injury. Production of the serine protease inhibitors (serpins) plasminogen activator inhibitor‐1 (PAI‐1) and protease nexin‐1 (PN‐1) by astrocytes may counterbalance excessive serine protease activity associated with CNS pathologies such as ischemic stroke. Knowledge regarding the regulation of these genes in the brain is limited, so the objective of the present study was to characterize the effects of injury‐related factors on serpin expression in human astrocytes. Native human astrocytes were exposed to hypoxia or cytokines, including interleukin‐6 (IL‐6), IL‐1β, tumor necrosis factor‐α (TNF‐α), IL‐10, transforming growth factor‐α (TGF‐α), and TGF‐β for 0–20 hr. Serpin mRNA expression and protein secretion were determined by real‐time RT‐PCR and ELISA, respectively. Localization of PAI‐1 and PN‐1 in human brain tissue was examined by immunohistochemistry. Hypoxia and all assayed cytokines induced a significant increase in PAI‐1 expression, whereas prolonged treatment with IL‐1β or TNF‐α resulted in a significant down‐regulation. The most pronounced induction of both PAI‐1 and PN‐1 was observed following early treatment with TGF‐α. In contrast to PAI‐1, the PN‐1 gene did not respond to hypoxia. Positive immunoreactivity for PAI‐1 in human brain tissue was demonstrated in reactive astrocytes within gliotic areas of temporal cortex. We show here that human astrocytes express PAI‐1 and PN‐1 and demonstrate that this astrocytic expression is regulated in a dynamic manner by injury‐related factors. © 2010 Wiley‐Liss, Inc.