title: 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.
abstract: Hepatic expression of CMP-NeuAc:Gal beta 1,4GlcNAc alpha 2,6-sialyltransferase (ST6Gal I) is induced as part of the acute phase response in mammals by mechanisms that remain poorly understood. Previous work suggests that murine 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 ST6Gal I mRNAs transcribed from the hepatic-specific promoter, P1. Exon H-containing ST6Gal I mRNA is expressed in all three mice strains examined: balb/c, C57B46, and 129Sv. Furthermore, murine RNA tissue survey indicates that presence of Exon H-containing transcripts is restricted to the liver. When mice are subjected to subcutaneous injection of turpentine to elicit the hepatic acute phase response, greater than 4-fold elevation in liver ST6Gal I mRNA was observed. Consistent with the view that Exon H-containing transcripts is regulated by the murine P1 promoter, 5'-RACE analysis indicates that the majority of these transcripts contains the Exon H sequence. This is consistent with the view that Exon H-containing transcripts are regulated by the murine P1 region. To assess the mechanism of ST6Gal I response in the hepatic acute phase reaction, mice harboring lesions in both alleles of the IL-6 gene were examined. IL-6(-/-) animals expressed normal levels of ST6Gal I mRNA in liver, with Exon H-containing transcripts remaining the predominant mRNA isoform. However, hepatic ST6Gal I is not elevated upon turpentine injection in the IL-6(-/-) animals. These results indicate that ST6Gal I induction in mouse liver during the acute phase reaction is mediated predominantly by the IL-6 pathway, and results in the induction of the Exon H-containing class of ST6Gal I mRNA that is specific to the liver.
authors.affiliation: Department of Molecular and Cellular Biology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
authors.forename: M
authors.initials: M
authors.lastname: Dalziel
authors.forename: S
authors.initials: S
authors.lastname: Lemaire
authors.forename: J
authors.initials: J
authors.lastname: Ewing
authors.forename: L
authors.initials: L
authors.lastname: Kobayashi
authors.forename: J T
authors.initials: JT
authors.lastname: Lau
mesh_terms: D000210:Acute-Phase Reaction / Q000201:enzymology* / Q000235:genetics* / Q000276:immunology; D000818:Animals; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D005091:Exons; D015870:Gene Expression; D006801:Humans; D015850:Interleukin-6 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D008099:Liver / Q000201:enzymology* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D012799:Sialyltransferases / Q000096:biosynthesis* / Q000235:genetics*; D013045:Species Specificity; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase
chemical_list: D017931:DNA Primers; D015850:Interleukin-6; D012333:RNA, Messenger; D012799:Sialyltransferases; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase