title: Suppression of miR-155 Expression in IFN-γ-Treated Astrocytes and Microglia by DJ-1: A Possible Mechanism for Maintaining SOCS1 Expression.
abstract: Previously, we reported that DJ-1, encoded by a Parkinson's disease (PD)-associated gene, inhibits expression of proinflammatory mediators in interferon-gamma (IFN-γ)-treated astrocytes and microglia through inhibition of STAT1 activation. Here, using microglia and astrocytes cultured from wild-type (WT) and DJ-1-knockout (KO) mouse brains, we examined how DJ-1 regulates suppressor of cytokine signaling 1 (SOCS1), a negative feedback regulator of STAT1 (signal transducer and activator of transcription) that is also induced by STAT1. We found that IFN-γ significantly increased SOCS1 mRNA expression in WT microglia and astrocytes, but not in KO cells, although STAT1 was highly activated in these latter cells. We further found that SOCS mRNA stability was decreased in DJ-1-KO cells, an effect that appeared to be mediated by the microRNA, miR-155. IFN-γ increased the levels of miR-155 in DJ-1-KO cells but not in WT cells. In addition, an miR-155 inhibitor rescued SOCS1 expression and decreased STAT1 activation in DJ-1-KO cells. Taken together, these results suggest that DJ-1 efficiently regulates inflammation by maintaining SOCS1 expression through regulation of miR-155 levels, even under conditions in which STAT1 activation is decreased.
authors: Department of Biomedical Sciences, Neuroscience Graduate Program, Ajou University School of Medicine, Suwon 443-380, Korea. ; Department of Pharmacology, Ajou University School of Medicine, Suwon 443-380, Korea. ; Department of Brain Science, Ajou University School of Medicine, Suwon 443-380, Korea. ; Chronic Inflammatory Disease Research Center, Ajou University School of Medicine, Suwon 443-380, Korea.
authors: Jong-Hyeon
authors: JH
authors: Kim
authors: Department of Biomedical Sciences, Neuroscience Graduate Program, Ajou University School of Medicine, Suwon 443-380, Korea. ; Department of Pharmacology, Ajou University School of Medicine, Suwon 443-380, Korea. ; Chronic Inflammatory Disease Research Center, Ajou University School of Medicine, Suwon 443-380, Korea.
authors: Ilo
authors: I
authors: Jou
authors: Department of Biomedical Sciences, Neuroscience Graduate Program, Ajou University School of Medicine, Suwon 443-380, Korea. ; Department of Pharmacology, Ajou University School of Medicine, Suwon 443-380, Korea. ; Department of Brain Science, Ajou University School of Medicine, Suwon 443-380, Korea. ; Chronic Inflammatory Disease Research Center, Ajou University School of Medicine, Suwon 443-380, Korea.
authors: Eun-Hye
authors: EH
authors: Joe
keywords: DJ-1; SOCS1; inflammation; miR-155; parkinson