IFN-α Enhances TLR3-Mediated Antiviral Cytokine Expression in Human Endothelial and Epithelial Cells by Up-Regulating TLR3 Expression

Abstract

TLRs play a critical role in early innate immune response to virus infection. TLR3 together with TLR7 and TLR8 constitute a powerful system to detect genetic material of RNA viruses. TLR3 has been shown to bind viral dsRNA whereas TLR7 and TLR8 are receptors for viral single-stranded RNA. In this report we show that TLR7 or TLR8 are not expressed in human epithelial A549 cells or in HUVECs. Accordingly, A549 cells and HUVECs were unresponsive to TLR7/8 ligand R848. TLR3 was expressed at a higher level in HUVECs than in A549 cells. The TLR3 ligand poly(I:C) up-regulated IFN-β, IL-28, IL-29, STAT1, and TLR3 expression in HUVECs but not in A549 cells. An enhanced TLR3 expression by transfection or by IFN-α stimulation conferred poly(I:C) responsiveness in A549 cells. Similarly, IFN-α pretreatment strongly enhanced poly(I:C)-induced activation of IFN-β, IL-28, and IL-29 genes also in HUVECs. In conclusion, our results suggest that IFN-α-induced up-regulation of TLR3 expression is involved in dsRNA activated antiviral response in human epithelial and endothelial cells.

Increased expression of Toll-like receptor 3 in intrahepatic biliary epithelial cells at sites of ductular reaction in diseased livers

“…In addition to these molecules involved in innate and acquired immune response, we here demonstrated for the first time that RIG-I/MDA5-MAVS signaling pathway is operative in the strong induction of IFN-b by dsRNA stimulation in HIBECs. TLR3 and RIG-I/MDA5 expression increase in the presence of IFN-a, IFN-b, IFN-c, and TNF-a in vitro [39][40][41][42][43]. These results may indicate that intrahepatic biliary epithelial cells are involved as an immunoregulatory organ in various liver diseases, including PBC, AIH, and CHC.…”

Immune Regulation by Microvascular Endothelial Cells: Directing Innate and Adaptive Immunity, Coagulation, and Inflammation

“…In the only report investigating the expression of TLR7 or TLR8 by ECs, neither TLR was found to be expressed in HUVECs (28). In contrast, TLR9 is spontaneously expressed by mouse and rat lung ECs, and exposure to CpG DNA induces an inflammatory response manifested by IL-8 and ICAM-1 induction through p38 MAPK-and NF-Bmediated pathways (35).…”

“…TLR3 is spontaneously present on HUVECs, and ligation by poly(I:C) up-regulates its expression together with that of IFN-␤, IL-28, IL-29, and STAT1 (28). TLR4 expression has been demonstrated on various ECs and significantly increases under inflammatory conditions.…”

The role of pattern recognition receptors in the innate recognition ofCandida albicans

“…89,90 Human umbilical vein endothelial cells (HUVECs) express TLR3 and TLR9. [91][92][93] Human dermal microvascular endothelial cells express MR. 94 Besides, Galection-3 was detected on cultured endothelial cells. 95 The expression of Dectin-1 on endothelial cells is controversial.…”