title: Pretreatment of LPS inhibits IFN-β-induced STAT1 phosphorylation through SOCS3 induced by LPS.
abstract: It has been known that LPS activates macrophages and induces IFN-β production from macrophages. The endogenous IFN-β produced by LPS stimulates the cells, which plays a role in innate immune. However, it was not elucidated yet if the signaling by exogenous IFN-β was influenced by LPS stimulation. In this study, it was found pretreatment of LPS interrupted IFN-β-induced JAK1/STAT1 phosphorylation. LPS pretreatment also reduced IFN-β-induced ISG54, one of IFN-β-inducible genes. Pretreatment with LPS for more than 2h shows inhibitory effect on IFN-β-induced STAT1 phosphorylation but simultaneous treatment or post-treatment of LPS with IFN-β did not show the inhibitory effect. The study using a neutralizing antibody to IFN-β indicated that IFN-β produced by LPS does not take part in the inhibitory effect of LPS. Furthermore, LPS did not affect the expression of IFN αβ receptor. A previous report has shown that LPS-induced SOCS3 inhibited IFN-γ-induced STAT1 phosphorylation, likewise, it was also shown in this study that LPS induced SOCS3 expression and its expression inhibited IFN-β-induced STAT1 phosphorylation which was confirmed by the knockdown study by the siRNA of SOCS3. The real-time PCR and immune-blot studies of SOCS3 indicated that LPS induced SOCS3 is independent of IL-6, IL-10, TNF-α and STAT3, and might depend on p38 activation by LPS. It was suggested that bacterial LPS rather interfere with IFN-β actions, dependent on the timing of LPS stimulation.
authors.affiliation: Department of Dermatology, Aichi Medical University school of Medicine, Nagakute, Aichi 480-1195, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Ando
authors.affiliation: Department of Microbiology and Immunology, Aichi Medical University School of Medicine, Nagakute, Aichi 480-1195, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Komatsu
authors.affiliation: Department of Microbiology and Immunology, Aichi Medical University School of Medicine, Nagakute, Aichi 480-1195, Japan.
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Naiki
authors.affiliation: Department of Microbiology and Immunology, Aichi Medical University School of Medicine, Nagakute, Aichi 480-1195, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Yokochi
authors.affiliation: Department of Dermatology, Aichi Medical University school of Medicine, Nagakute, Aichi 480-1195, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Watanabe
authors.affiliation: Department of Microbiology and Immunology, Aichi Medical University School of Medicine, Nagakute, Aichi 480-1195, Japan. Electronic address: koide@aichi-med-u.ac.jp.
authors.forename: Naoki
authors.initials: N
authors.lastname: Koide
mesh_terms: D000818:Animals; D002460:Cell Line; D005786:Gene Expression Regulation / Q000187:drug effects; D055785:Gene Knockdown Techniques; D016899:Interferon-beta / Q000008:administration & dosage / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D010766:Phosphorylation / Q000187:drug effects; D034741:RNA, Small Interfering / Q000008:administration & dosage; D060888:Real-Time Polymerase Chain Reaction; D050794:STAT1 Transcription Factor / Q000378:metabolism*; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors
chemical_list: D008070:Lipopolysaccharides; D034741:RNA, Small Interfering; D050794:STAT1 Transcription Factor; C491411:Socs3 protein, mouse; C494080:Stat1 protein, mouse; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D016899:Interferon-beta
keywords: IFN-β; LPS; SOCS3; STAT1