374 S100B Binding to Toll-Like Receptor 4 Induces the Proinflammatory Cytokines Tumor Necrosis Factor Alpha and Interleukin 6 Post-Myocardial Infarction

2012 ◽  
Vol 28 (5) ◽  
pp. S238
Author(s):  
J. Tsoporis ◽  
J. Desjardins ◽  
G. Proteau ◽  
S. Izhar ◽  
T.G. Parker
Keyword(s):  
Myocardial Infarction ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Proinflammatory Cytokines ◽  
Tumor Necrosis ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Necrosis Factor

scholarly journals Tumor Necrosis Factor Alpha Transcription in Macrophages Is Attenuated by an Autocrine Factor That Preferentially Induces NF-κB p50

1998 ◽  
Vol 18 (10) ◽  
pp. 5678-5689 ◽  
Author(s):  
Mark Baer ◽  
Allan Dillner ◽  
Richard C. Schwartz ◽  
Constance Sedon ◽  
Sergei Nedospasov ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Proinflammatory Cytokines ◽  
Tumor Necrosis ◽  
Transforming Growth Factor ◽  
Tumor Cell Line ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Factor Alpha ◽  
Necrosis Factor

ABSTRACT Macrophages are a major source of proinflammatory cytokines such as tumor necrosis factor alpha (TNF-α), which are expressed during conditions of inflammation, infection, or injury. We identified an activity secreted by a macrophage tumor cell line that negatively regulates bacterial lipopolysaccharide (LPS)-induced expression of TNF-α. This activity, termed TNF-α-inhibiting factor (TIF), suppressed the induction of TNF-α expression in macrophages, whereas induction of three other proinflammatory cytokines (interleukin-1β [IL-1β], IL-6, and monocyte chemoattractant protein 1) was accelerated or enhanced. A similar or identical inhibitory activity was secreted by IC-21 macrophages following LPS stimulation. Inhibition of TNF-α expression by macrophage conditioned medium was associated with selective induction of the NF-κB p50 subunit. Hyperinduction of p50 occurred with delayed kinetics in LPS-stimulated macrophages but not in fibroblasts. Overexpression of p50 blocked LPS-induced transcription from a TNF-α promoter reporter construct, showing that this transcription factor is an inhibitor of the TNF-α gene. Repression of the TNF-α promoter by TIF required a distal region that includes three NF-κB binding sites with preferential affinity for p50 homodimers. Thus, the selective repression of the TNF-α promoter by TIF may be explained by the specific binding of inhibitory p50 homodimers. We propose that TIF serves as a negative autocrine signal to attenuate TNF-α expression in activated macrophages. TIF is distinct from the known TNF-α-inhibiting factors IL-4, IL-10, and transforming growth factor β and may represent a novel cytokine.

Sign in / Sign up

Export Citation Format

Share Document