title: Regulation of the Expression of Heparan Sulfate 3-O-Sulfotransferase 3B (HS3ST3B) by Inflammatory Stimuli in Human Monocytes.
abstract: Heparan sulfate (HS) is recognized as an important player in a wide range of dynamic steps of inflammatory reactions. Thereby, structural HS remodeling is likely to play an important role in the regulation of inflammatory and immune responses; however, little is known about underlying mechanism. In this study, we analyzed the regulation of expression of HS 3-O-sulfotransferases (HS3STs) in response to inflammatory stimuli. We found that among the seven HS3ST isoenzymes, only the expression of HS3ST3B was markedly up-regulated in human primary monocytes and the related cell line THP1 after exposure to TLR agonists. TNF-α was also efficient, to a lesser extent, to increase HS3ST3B expression, while IL-6, IL-4, and IFN-γ were poor inducers. We then analyzed the molecular mechanisms that regulate the high expression of HS3ST3B in response to LPS. Based on the expression of HS3ST3B transcripts and on the response of a reporter gene containing the HS3ST3B1 promoter, we provide evidence that LPS induces a rapid and strong transcription of HS3ST3B1 gene, which was mainly dependent on the activation of NF-κB and JNK signaling pathways. Additionally, active p38 MAPK and de novo synthesized proteins are involved in post-transcriptional mechanisms to maintain a high level of HS3ST3B mRNA to a steady state. Altogether, our findings indicate that HS3ST3B1 gene behaves as a primary response gene, suggesting that it may play an important role in making 3-O-sulfated HS with specific functions in the regulation of inflammatory and immune responses. J. Cell. Biochem. 117: 1529-1542, 2016. © 2015 Wiley Periodicals, Inc.
authors.affiliation: Université Lille, CNRS, UMR 8576-UGSF-Unité de Glycobiologie Structurale et Fonctionnelle, F-59000, Lille, France.
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Sikora
authors.affiliation: Université Lille, CNRS, UMR 8576-UGSF-Unité de Glycobiologie Structurale et Fonctionnelle, F-59000, Lille, France.
authors.forename: Maxime
authors.initials: M
authors.lastname: Delos
authors.affiliation: Université Lille, CNRS, UMR 8576-UGSF-Unité de Glycobiologie Structurale et Fonctionnelle, F-59000, Lille, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Martinez
authors.affiliation: Université Lille, CNRS, UMR 8576-UGSF-Unité de Glycobiologie Structurale et Fonctionnelle, F-59000, Lille, France.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Carpentier
authors.affiliation: Université Lille, CNRS, UMR 8576-UGSF-Unité de Glycobiologie Structurale et Fonctionnelle, F-59000, Lille, France.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Allain
authors.affiliation: Université Lille, CNRS, UMR 8576-UGSF-Unité de Glycobiologie Structurale et Fonctionnelle, F-59000, Lille, France.
authors.forename: Agnès
authors.initials: A
authors.lastname: Denys
mesh_terms: D045744:Cell Line, Tumor; D016207:Cytokines / Q000096:biosynthesis; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D008070:Lipopolysaccharides / Q000633:toxicity*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D009000:Monocytes / Q000201:enzymology* / Q000473:pathology; D020871:RNA Stability / Q000187:drug effects*; D015238:Sulfotransferases / Q000096:biosynthesis*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; D048051:p38 Mitogen-Activated Protein Kinases; D015238:Sulfotransferases
keywords: 3-O-SULFOTRANSFERASE; GENE REGULATION; HEPARAN SULFATE; INFLAMMATION