Effect of gamma interferon on cachectin expression by mononuclear phagocytes. Reversal of the lpsd (endotoxin resistance) phenotype

doi:10.1084/jem.164.5.1791

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Effect of gamma interferon on cachectin expression by mononuclear phagocytes. Reversal of the lpsd (endotoxin resistance) phenotype

B Beutler, V Tkacenko, I Milsark, N Krochin and A Cerami

IFN-gamma permits the endotoxin-induced production of cachectin by C3H/HeJ (endotoxin resistant) macrophages, apparently by facilitating endotoxin-induced cachectin biosynthesis at both transcriptional and posttranscriptional levels. IFN-gamma cannot induce cachectin biosynthesis by itself, nor does it markedly enhance cachectin production by endotoxin-induced peritoneal macrophages obtained from endotoxin-responsive mice. Elucidation of the precise mechanism through which IFN-gamma influences cachectin biosynthesis may permit a better understanding of the molecular events that follow endotoxin-induced activation of macrophages. Moreover, the permissive effect of IFN-gamma on cachectin biosynthesis might elicit enhanced endotoxin sensitivity in vivo.
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