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Springer, Dordrecht

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10.1002/anie.201412493

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The Physiology of the Acute Phase Serum Amyloid a (SAA) Response in Mice

Authors: J. D. Sipe, R. Neta, P. Ghezzi, R. Numerof,

Publish Date: 1991
Volume: , Issue:, Pages: 71-74
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Abstract

LPS stimulates the mononuclear phagocyte system to produce interleukin 1 (IL-1) and tumor necrosis factor (TNF) which in turn activate the murine serum amyloid A gene family to result in synthesis of apo-SAA isoforms. The molecular mechanism by which purified recombinant IL-1 regulates the quantity of apo-SAA production was investigated in CD2F1, C3H/HeJ and CDl mice. Three observations support a physiological role for IL-1 in regulation of SAA gene expression: 1) Monoclonal antibodies to the EL-4 IL-1 receptor significantly inhibited IL-1 induced SAA production; 2) The recombinant IL-1 receptor antagonist (IL-lra) completely blocked IL-1 induced SAA mRNA transcription; and 3) The calcium antagonist chlorprcmazine inhibited LPS, IL-1 and TNF induced SAA synthesis. Phorbol myristate acetate (PMA) stimulated SAA production maximally at 6 rather than 24 hours, a time course more similar to IL-1 and TNF than to LPS. Repeated administration of PMA resulted in tolerance (reduced capacity for SAA production) to further stimulation with either PMA or LPS suggesting the two agents share a pathway of signal transduction to the transcriptional machinery of the SAA gene family.


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