The Physiology of the Acute Phase Serum Amyloid a

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 IL1 and tumor necrosis factor TNF which in turn activate the murine serum amyloid A gene family to result in synthesis of apoSAA isoforms The molecular mechanism by which purified recombinant IL1 regulates the quantity of apoSAA production was investigated in CD2F1 C3H/HeJ and CDl mice Three observations support a physiological role for IL1 in regulation of SAA gene expression 1 Monoclonal antibodies to the EL4 IL1 receptor significantly inhibited IL1 induced SAA production 2 The recombinant IL1 receptor antagonist ILlra completely blocked IL1 induced SAA mRNA transcription and 3 The calcium antagonist chlorprcmazine inhibited LPS IL1 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 IL1 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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