RRC ID 38886
Author Ando T, Komatsu T, Naiki Y, Yokochi T, Watanabe D, Koide N.
Title Pretreatment of LPS inhibits IFN-β-induced STAT1 phosphorylation through SOCS3 induced by LPS.
Journal Biomed Pharmacother
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.
Volume 76
Pages 1-5
Published 2015-12-1
DOI 10.1016/j.biopha.2015.10.019
PII S0753-3322(15)00237-1
PMID 26653542
MeSH Animals Cell Line Gene Expression Regulation / drug effects Gene Knockdown Techniques Interferon-beta / administration & dosage Interferon-beta / pharmacology* Lipopolysaccharides / pharmacology* Macrophages / drug effects Macrophages / metabolism Mice Phosphorylation / drug effects RNA, Small Interfering / administration & dosage Real-Time Polymerase Chain Reaction STAT1 Transcription Factor / metabolism* Suppressor of Cytokine Signaling 3 Protein Suppressor of Cytokine Signaling Proteins / genetics Suppressor of Cytokine Signaling Proteins / metabolism* Time Factors
IF 3.743
Times Cited 3
Human and Animal Cells RAW 264(RCB0535)