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Components of the Plasminogen Activator System in Astrocytes Are Modulated by Tumor Necrosis Factor‐α and Interleukin‐1β Through Similar Signal Transduction Pathways
Author(s) -
FaberElman Anat,
Miskin Ruth,
Schwartz Michal
Publication year - 1995
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1995.65041524.x
Subject(s) - signal transduction , plasminogen activator , proinflammatory cytokine , biology , cycloheximide , cytokine , calphostin c , tissue plasminogen activator , microbiology and biotechnology , plasminogen activator inhibitor 1 , tumor necrosis factor alpha , fibrinolysis , interleukin , inflammation , endocrinology , protein kinase c , medicine , biochemistry , immunology , protein biosynthesis
Migration of astrocytes is thought to play a role in nerve regeneration and to be mediated, at least in part, by inflammation‐associated cytokines. Plasminogen activators are secreted proteases that function in fibrinolysis and participate in cellular migration and invasion and, in some cases, are modulated by cytokines. Here, we show that two cytokines, tumor necrosis factor‐α and interleukin‐1β, can modulate plasminogen activation in astrocytes, each causing 90% reduction of total plasminogen activator activity. Direct and reverse zymography indicated that this reduction resulted from two simultaneous events, a pronounced decrease in tissue‐type plasminogen activator activity and an induction of plasminogen activator inhibitor‐1. Northern hybridization analysis indicated a 30‐fold increase of the steady‐state level of plasminogen activator inhibitor‐1 mRNA following treatment with each of the two cytokines. Both of the cytokine‐induced effects could be blocked by cycloheximide or actinomycin D. When signal transduction pathways were blocked, the results indicated the involvement of reduction in cyclic AMP levels, protein kinase activity, and arachidonic metabolites of the lipoxygenase pathway. The results thus show that the two cytokines reduce the ability of astrocytes to conduct fibrinolysis and extracellular proteolysis, and suggest that the effect of these cytokines on members of the plasminogen activation system is through a common signal transduction pathway.