PRIMING DOES NOT CHANGE PROMOTER SEQUENCE REQUIREMENTS FOR IFN INDUCTION OR CORRELATE WITH THE EXPRESSION OF IFN REGULATORY FACTOR-I

Pretreatment of L929 cells with IFN enhances Sendai virus-mediated ind uction of IL-6, TNF-alpha, and IFNA and IFNB genes. The priming effect could be demonstrated at both the RNA and protein levels and the form er did not require cellular protein synthesis. Priming increased the S endai virus-mediated induction of a murine IFNA4 promoter-chlorampheni col acetyltransferase gene hybrid plasmid (A4CAT) in transiently trans fected cells, and deletion analysis showed that the identical DNA sequ ence was required for the inducibility in primed and unprimed cells. C otransfection of A4 CAT plasmid with interferon regulatory factor-1 (I RF-1) expression plasmid increased CAT expression, however, the IRF-1- mediated expression was further enhanced by priming. These results sho w that the identical inducible element present in the promoter region of IFNA4 gene is required for both the inducibility and the priming ef fect; however, no direct correlation between the enhancement of expres sion of the IRF-1 gene and enhancement of expression of IFN, IL-6, and TNF-alpha genes in the primed cells was observed. We suggest that pri ming facilitates inducer-mediated posttranscriptional modulation of va rious transcriptional factors that play a role in stimulation of trans cription of these genes.