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 bo play a role in various neurodenegerative diseases. The interaction of these two cytokines, however, is unknown. We tested the hypothesis that the TNF-alpha released from lipopolysaccharide (LPS)-treated murine microglial cells would stimulate the release of TGF-beta, which in turn would control TNF-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 48 hr). Anti-TNF-alpha 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 cell expression of TGF-beta 1 mRNA and release of TGF-beta. Exogenous TGF-beta, on the other hand, suppressed LPS-stimulated TNF-alpha release. These findings suggest an autoregulation of microglial cell TNF-alpha production by TGF-beta which may limit inflammation-associated brain injury.
Chao
C C
CC
Minneapolis Medical Research Foundation, Department of Medicine, Hennepin County Medical Center, Minnesota, USA.
Hu
S
S
Sheng
W S
WS
Tsang
M
M
Peterson
P K
PK
D000818:Animals; D000831:Animals, Newborn; D000911:Antibodies, Monoclonal / Q000276:immunology; D001483:Base Sequence; D002478:Cells, Cultured; D017931:DNA Primers / Q000737:chemistry; D015342:DNA Probes / Q000737:chemistry; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D017628:Microglia / Q000378:metabolism*; D008969:Molecular Sequence Data; D010431:Pentoxifylline / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D016212:Transforming Growth Factor beta / Q000096:biosynthesis* / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000276:immunology / Q000502:physiology*
D000911:Antibodies, Monoclonal; D017931:DNA Primers; D015342:DNA Probes; D008070:Lipopolysaccharides; D010726:Phosphodiesterase Inhibitors; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D010431:Pentoxifylline