Hepatic acute phase induction of murine beta-galactoside alpha 2,6 sialyltransferase (ST6Gal I) is IL-6 dependent and mediated by elevation of Exon H-containing class of transcripts.

Hepatic expression of CMP-NeuAc:Gal beta 1,4GlcNAc alpha 2,6-sialyltransfer ase (ST6Gal I) is induced as part of the acute phase response in mammals by mechanisms that remain poorly understood. Previous work suggests that muri ne liver ST6Gal I mRNA contains an additional and novel region that is not found on ST6Gal I mRNA from human HepG2 hepatoma cells and from rat liver. This novel region, residing 5' of the common Exon I sequence, is encoded by a discrete upstream exon, Exon H, Here we provide evidence that the Exon H -containing transcript is the murine counterpart of the human and rat ST6Ga l I mRNAs transcribed from the hepatic-specific promoter, P1. Exon H-contai ning ST6Gal I mRNA is expressed in all three mice strains examined: balb/c, C57B46, and 129Sv. Furthermore, murine RNA tissue survey indicates that pr esence of Exon H-containing transcripts is restricted to the liver. When mi ce are subjected to subcutaneous injection of turpentine to elicit the hepa tic acute phase response, greater than 4-fold elevation in liver ST6Gal I m RNA was observed. Consistent with the view that Exon H-containing transcrip ts is regulated by the murine P1 promoter, 5'-RACE analysis indicates that the majority of these transcripts contains the Exon H sequence, This is con sistent with the view that Exon H-containing transcripts are regulated by t he murine P1 region. To assess the mechanism of ST6Gal I response in the he patic acute phase reaction, mice harboring lesions in both alleles of the I L-6 gene were examined. IL-6(-/-) animals expressed normal levels of ST6Gal I mRNA in liver, with Exon H-containing transcripts remaining the predomin ant mRNA isoform, However, hepatic ST6Gal I is not elevated upon turpentine injection in the IL-6(-/-) animals. These results indicate that ST6Gal I i nduction in mouse liver during the acute phase reaction is mediated predomi nantly by the IL-6 pathway, and results in the induction of the Exon H-cont aining class of ST6Gal I mRNA that is specific to the liver.