+ Site Statistics
References:
54,258,434
Abstracts:
29,560,870
PMIDs:
28,072,757
+ Search Articles
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ PDF Full Text
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Translate
+ Recently Requested

Stimulation of nuclear receptor REV-ERBs regulates tumor necrosis factor-induced expression of proinflammatory molecules in C6 astroglial cells



Stimulation of nuclear receptor REV-ERBs regulates tumor necrosis factor-induced expression of proinflammatory molecules in C6 astroglial cells



Biochemical and Biophysical Research Communications 469(2): 151-157



Under physiological conditions, astrocytes maintain homeostasis in the CNS. Following inflammation and injury to the CNS, however, activated astrocytes produce neurotoxic molecules such as cytokines and chemokines, amplifying the initial molecular-cellular events evoked by inflammation and injury. Nuclear receptors REV-ERBα and REV-ERBβ (REV-ERBs) are crucial in the regulation of inflammation- and metabolism-related gene transcription. The current study sought to elucidate a role of REV-ERBs in rat C6 astroglial cells on the expression of inflammatory molecules following stimulation with the neuroinflammatory cytokine tumor necrosis factor (TNF). Stimulation of C6 cells with TNF (10 ng/ml) significantly increased the mRNA expression of CCL2, interleukin-6 (IL-6), inducible nitric oxide synthase (iNOS), and matrix metalloprotease (MMP)-9, but not fibroblast growth factor-2 (FGF-2), cyclooxygenase-2 (COX-2) and MMP-2. Treatment with either REV-ERB agonists GSK4112 or SR9009 significantly blocked TNF-induced upregulation of CCL2 mRNA and MMP-9 mRNA, but not IL-6 mRNA and iNOS mRNA expression. Furthermore, treatment with RGFP966, a selective histone deacetylase 3 (HDAC3) inhibitor, potently reversed the inhibitory effects of GSK4112 on TNF-induced expression of MMP-9 mRNA, but not CCL2 mRNA. Expression of Rev-erbs mRNA in C6 astroglial cells, primary cultured rat cortical and spinal astrocytes was confirmed by reverse transcription polymerase chain reaction. Together, the findings demonstrate an anti-inflammatory effect, downregulating of MMP-9 and CCL2 transcription, of astroglial REV-ERBs activation through HDAC3-dependent and HDAC3-independent mechanisms.

(PDF emailed within 0-6 h: $19.90)

Accession: 058905949

Download citation: RISBibTeXText

PMID: 26616049

DOI: 10.1016/j.bbrc.2015.11.086


Related references

Nuclear factor of activated T cells negatively regulates expression of the tumor necrosis factor receptor-related 2 gene in T cells. Experimental and Molecular Medicine 42(12): 805-810, 2011

Aqueous extract of Salvia miltiorrhoza regulates adhesion molecule expression of tumor necrosis factor alpha-induced endothelial cells by blocking activation of nuclear factor kappaB. Journal of Cardiovascular Pharmacology 45(6): 516-524, 2005

Activation-induced tumor necrosis factor receptor-associated factor 3 (Traf3) alternative splicing controls the noncanonical nuclear factor κB pathway and chemokine expression in human T cells. Journal of Biological Chemistry 289(19): 13651-13660, 2014

Involvement of the nuclear factor-κB signaling pathway in the regulation of CXC chemokine receptor-4 expression in neuroblastoma cells induced by tumor necrosis factor-α. International Journal of Molecular Medicine 35(2): 349-357, 2015

Berberine inhibits tumor necrosis factor-α-induced expression of inflammatory molecules and activation of nuclear factor-κB via the activation of AMPK in vascular endothelial cells. Molecular Medicine Reports 12(4): 5580-5586, 2016

Preferential expression of tumor necrosis factor receptor 55 (TNF-R55) on human articular chondrocytes: selective transcriptional upregulation of TNF-R75 by proinflammatory cytokines interleukin 1beta, tumor necrosis factor-alpha, and basis fibroblast growth factor. Journal of Rheumatology 26(3): 645-653, 1999

Effects of inhibitors of transcription factors, nuclear factor-κB and activator protein 1, on the expression of proinflammatory cytokines and chemokines induced by stimulation with Toll-like receptor ligands in hen vaginal cells. Poultry Science 96(3): 723-730, 2017

Activation of nuclear factor-κB pathway is responsible for tumor necrosis factor-α-induced up-regulation of endothelin B2 receptor expression in vascular smooth muscle cells in vitro. Toxicology Letters 209(2): 107-112, 2012

Nuclear factor of activated T cells c1 induces osteoclast-associated receptor gene expression during tumor necrosis factor-related activation-induced cytokine-mediated osteoclastogenesis. Journal of Biological Chemistry 280(42): 35209-35216, 2005

Dihydrotestosterone inhibits interleukin-1α or tumor necrosis factor α-induced proinflammatory cytokine production via androgen receptor-dependent inhibition of nuclear factor-κB activation in rheumatoid fibroblast-like synovial cell line. Biological and Pharmaceutical Bulletin 34(11): 1724-1730, 2012

Dihydrotestosterone Inhibits Interleukin-1a or Tumor Necrosis Factor a-Induced Proinflammatory Cytokine Production via Androgen Receptor-Dependent Inhibition of Nuclear Factor-B Activation in Rheumatoid Fibroblast-Like Synovial Cell Line. Biological & Pharmaceutical Bulletin 34(11): 1724-1730, 2011

Myosin light chain kinase expression induced via tumor necrosis factor receptor 2 signaling in the epithelial cells regulates the development of colitis-associated carcinogenesis. Plos One 9(2): E88369, 2014

The expression of inducible nitric oxide synthase in human retinal pigment epithelial cells under stimulation of proinflammatory cytokine tumor necrosis factor-?. Taiwan Journal of Ophthalmology 2(1): 0-17, 2012

Polaprezinc down-regulates proinflammatory cytokine-induced nuclear factor-kappaB activiation and interleukin-8 expression in gastric epithelial cells. Journal of Pharmacology and Experimental Therapeutics 291(1): 345-352, 1999

Nuclear tumor necrosis factor receptor-associated factor 6 in lymphoid cells negatively regulates c-Myb-mediated transactivation through small ubiquitin-related modifier-1 modification. Journal of Biological Chemistry 283(8): 5081-5089, 2007