Expression of Plasminogen Activator Inhibitor-1 and Protease Nexin-1 in Human Astrocytes: Response to Injury-Related Factors.

• 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-1beta, tumor necrosis factor-alpha (TNF-alpha), IL-10, transforming growth factor-alpha (TGF-alpha), and TGF-beta 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-1beta or TNF-alpha resulted in a significant down-regulation. The most pronounced induction of both PAI-1 and PN-1 was observed following early treatment with TGF-alpha. 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Fysiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Physiology (hsv//eng)

Nyckelord

Amyloid beta-Protein Precursor

biosynthesis

Astrocytes

metabolism

Brain Chemistry

Brain Injuries

metabolism

pathology

Cell Hypoxia

Cells

Cultured

Cytokines

biosynthesis

Enzyme-Linked Immunosorbent Assay

Gene Expression

physiology

Glial Fibrillary Acidic Protein

biosynthesis

genetics

Humans

Hypoxia

Brain

pathology

Immunohistochemistry

Plasminogen Activator Inhibitor 1

biosynthesis

Protease Nexins

RNA

Messenger

biosynthesis

genetics

Receptors

Cell Surface

biosynthesis

Serpin E2

Serpins

biosynthesis

Tumor Necrosis Factor-alpha

metabolism

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)