TUMOR-NECROSIS-FACTOR-ALPHA MEDIATES THE RELEASE OF BIOACTIVE TRANSFORMING GROWTH-FACTOR-BETA IN MURINE MICROGLIAL CELL-CULTURES

Tumor necrosis factor (TNF)-alpha and transforming growth factor (TGF) -beta produced by glial cells have been proposed to play a role in var ious neurodegenerative diseases. The interaction of these two cytokine s, however, is unknown. We tested the hypothesis that the TNF-alpha re leased from lipopolysaccharide (LPS)-treated murine microglial cells w ould stimulate the release of TGF-beta, which in turn would control TN F-alpha production. Treatment of murine microglial cell cultures with LPS resulted in an acute release of TNF-alpha (peak by 8 hr) followed by delayed release of bioactive TGF-beta (peak by 8 hr). Anti-TNF-alph a antibody significantly inhibited LPS-stimulated TGF-beta production, suggesting the involvement of TNF-alpha in TGF-beta production. Also, exogenous TNF-alpha induced in a dose-dependent fashion microglial ce ll expression of TGF-beta 1 mRNA and release of TGF-beta. Exogenous TG F-beta, on the other hand, suppressed LPS-stimulated TNF-alpha release . These findings suggest an autoregulation of microglial cell TNF-alph a production by TGF-beta which may limit inflammation-associated brain injury. (C) 1995 Academic Press, Inc.