Double-stranded RNA induces galectin-9 in vascular endothelial cells: involvement of TLR3, PI3K, and IRF3 pathway.
Galectin-9 is a member of the galectin family, which induces various biological reactions such as chemotaxis of eosinophils and apoptosis of T cells. We previously reported that polyinosinic-polycytidylic acid (poly IC), an authentic double-stranded RNA (dsRNA), induces the expression of galectin-9 in human umbilical vein endothelial cells (HUVECs). In the present study, we addressed the possible involvement of two potential receptors for dsRNA, Toll-like receptor (TLR) 3 and retinoic acid-inducible gene-I (RIG-I), in the expression of galectin-9 in HUVECs. Poly IC-induced galectin-9 expression was almost completely suppressed by RNA interference (RNAi) against TLR3, but not against RIG-I. LY294002, an inhibitor of phosphatidylinositol 3-kinase (PI3K), inhibited the induction of galectin-9 by poly IC. RNAi against interferon regulatory factor 3 (IRF3) also inhibited poly IC-induced galectin-9 expression. We conclude that TLR3, PI3K, and IRF3 are involved in the poly IC-induced galectin-9 expression in HUVECs.
Imaizumi
Tadaatsu
T
Department of Vascular Biology, Hirosaki University School of Medicine, Hirosaki, Japan. timaizum@cc.hirosaki-u.ac.jp
Yoshida
Hidemi
H
Nishi
Nozomu
N
Sashinami
Hiroshi
H
Nakamura
Takanori
T
Hirashima
Mitsuomi
M
Ohyama
Chikara
C
Itoh
Ken
K
Satoh
Kei
K
D002867:Chromones / Q000494:pharmacology; D042783:Endothelial Cells / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D037161:Galectins / Q000096:biosynthesis*; D005786:Gene Expression Regulation; D006801:Humans; D050838:Interferon Regulatory Factor-3 / Q000096:biosynthesis*; D008954:Models, Biological; D009025:Morpholines / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000096:biosynthesis*; D034622:RNA Interference; D012330:RNA, Double-Stranded / Q000737:chemistry*; D051196:Toll-Like Receptor 3 / Q000096:biosynthesis*; D014471:Umbilical Veins / Q000378:metabolism
D002867:Chromones; D004791:Enzyme Inhibitors; D037161:Galectins; C494232:IRF3 protein, human; D050838:Interferon Regulatory Factor-3; C105032:LGALS9 protein, human; D009025:Morpholines; D012330:RNA, Double-Stranded; D051196:Toll-Like Receptor 3; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D019869:Phosphatidylinositol 3-Kinases