Pretreatment of LPS inhibits IFN-β-induced STAT1 phosphorylation through SOCS3 induced by LPS

It has been known that LPS activates macrophages and induces IFN-beta production from macrophages. The endogenous IFN-beta 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-beta was influenced by LPS stimulation. In this study, it was found pretreatment of LPS interrupted IFN-beta-induced JAK1/STAT1 phosphorylation. LPS pretreatment also reduced IFN-beta-induced ISG54, one of IFN-beta-inducible genes. Pretreatment with LPS for more than 2 h shows inhibitory effect on IFN-beta-induced STAT1 phosphorylation but simultaneous treatment or post-treatment of LPS with IFN-beta did not show the inhibitory effect. The study using a neutralizing antibody to IFN-beta indicated that IFN-beta produced by LPS does not take part in the inhibitory effect of LPS. Furthermore, LPS did not affect the expression of IFN alpha beta receptor. A previous report has shown that LPS-induced SOCS3 inhibited IFN-gamma-induced STAT1 phosphorylation, likewise, it was also shown in this study that LPS induced SOCS3 expression and its expression inhibited IFN-beta-induced STAT1 phosphorylation which was confirmed by the knockdown study by the siRNA of SOCS3. The realtime PCR and immune-blot studies of SOCS3 indicated that LPS induced SOCS3 is independent of IL-6, IL10, TNF-alpha and STAT3, and might depend on p38 activation by LPS. It was suggested that bacterial LPS rather interfere with IFN-beta actions, dependent on the timing of LPS stimulation. (C) 2015 Elsevier Masson SAS. All rights reserved.