title: Suppression of IP-10/CXCL10 gene expression in LPS- and/or IFN-γ-stimulated macrophages by parasite-secreted products.
abstract: T helper (Th)2 polarized immune responses are characteristically dominant in helminth infections. The gene expression of interferon (IFN)-γ-inducible protein 10 (IP-10/CXCL10), which promotes Th1 responses, in mouse macrophages stimulated with lipopolysaccharide (LPS) and/or IFN-γ was suppressed by excretory/secretory (ES) products of Spirometra erinaceieuropaei plerocercoids. ES products suppressed LPS- and/or IFN-γ-induced transcriptional activities of a luciferase reporter gene under the control of a 243-bp fragment of the IP-10 gene promoter/enhancer, which contains an IFN-stimulated response element (ISRE) and two κB elements. Consistent with this result, ES products inhibited ISRE-dependent heterologous promoter activities and LPS- or IFN-γ-induced ISRE-binding activity. ES products also suppressed LPS-induced IFN-β gene expression. Furthermore, ES products suppressed nuclear factor (NF)-κB RelA (p65)-dependent transcriptional activity, whereas ES products had no effect on the κB-binding activity. These results suggest that ES products suppress the IP-10 gene expression by inhibiting the ISRE- and RelA-dependent transcriptional activities in mouse macrophages.
authors.affiliation: Division of Medical Zoology, Department of Microbiology and Immunology, Faculty of Medicine, Tottori University, 86 Nishi-cho, Yonago, Tottori 683-8503, Japan. fukumoto@med.tottori-u.ac.jp
authors.forename: Soji
authors.initials: S
authors.lastname: Fukumoto
authors.forename: Miki
authors.initials: M
authors.lastname: Hiroi
authors.forename: Paramasari
authors.initials: P
authors.lastname: Dirgahayu
authors.forename: Kazutoyo
authors.initials: K
authors.lastname: Miura
authors.forename: Sayuri
authors.initials: S
authors.lastname: Tademoto
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Otsuki
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Ohmori
mesh_terms: D000818:Animals; D002460:Cell Line; D054357:Chemokine CXCL10 / Q000235:genetics / Q000276:immunology*; D015536:Down-Regulation; D007371:Interferon-gamma / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology*; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D020218:Response Elements; D050794:STAT1 Transcription Factor / Q000276:immunology; D013146:Spirometra / Q000276:immunology*
chemical_list: D054357:Chemokine CXCL10; C485433:Cxcl10 protein, mouse; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D050794:STAT1 Transcription Factor; C494080:Stat1 protein, mouse; D007371:Interferon-gamma