Retinoic acid-inducible gene-I mediates RANTES/CCL5 expression in U373MG human astrocytoma cells stimulated with double-stranded RNA.
Retinoic acid-inducible gene-I (RIG-I) mediates part of the cell signaling in response to viral infection. Polyinosinic-polycytidilic acid (poly IC) is a synthetic double-stranded RNA (dsRNA) and mimics viral infection when applied to cell cultures. The CC chemokine, RANTES (regulated on activation, normal T-cell expressed and secreted), is a potent attractant for inflammatory cells such as memory T-lymphocytes, monocytes and eosinophils. In the present study, we demonstrated that poly IC enhances the expression of RIG-I in U373MG human astrocytoma cells. The RNA interference of RIG-I resulted in the suppression of the poly IC-induced RANTES expression. Pretreatment of the cells with SB203580, an inhibitor of p38 mitogen-activated protein kinase, and dexamethasone inhibited the poly IC-induced expression of RIG-I. Furthermore, poly IC upregulated RIG-I in normal human astrocytes in culture and the in vivo injection of poly IC into the striatum of the mouse brain induced the expression of RIG-I in astrocytes. We conclude that RIG-I may be involved in immune reactions against viral infection, at least in part, through the regulation of RANTES expression in astrocytes.
Yoshida
Hidemi
H
Department of Vascular Biology, Institute of Brain Science, Hirosaki University School of Medicine, 5 Zaifu-cho, Hirosaki 036-8562, Japan. hidemiyo@cc.hirosaki-u.ac.jp
Imaizumi
Tadaatsu
T
Lee
Sung Joong
SJ
Tanji
Kunikazu
K
Sakaki
Hirotaka
H
Matsumiya
Tomoh
T
Ishikawa
Akira
A
Taima
Kageaki
K
Yuzawa
Ei
E
Mori
Fumiaki
F
Wakabayashi
Koichi
K
Kimura
Hiroto
H
Satoh
Kei
K
D001254:Astrocytoma / Q000378:metabolism*; D045744:Cell Line, Tumor; D018946:Chemokine CCL5 / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D015870:Gene Expression / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007369:Interferon Inducers / Q000494:pharmacology; D011070:Poly I-C / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D012330:RNA, Double-Stranded / Q000494:pharmacology*; D013997:Time Factors; D015534:Trans-Activators; D014157:Transcription Factors / Q000378:metabolism*
D018946:Chemokine CCL5; D004791:Enzyme Inhibitors; D005904:Glial Fibrillary Acidic Protein; D007093:Imidazoles; D007369:Interferon Inducers; D011725:Pyridines; C431552:RAI1 protein, human; D012330:RNA, Double-Stranded; D015534:Trans-Activators; D014157:Transcription Factors; D011070:Poly I-C; C093642:SB 203580