Biochemical and Biophysical Research Communications, Vol.478, No.4, 1528-1533, 2016
Knockdown of FSTL1 inhibits oxLDL-induced inflammation responses through the TLR4/MyD88/NF-kappa B and MAPK
Activation of inflammation by oxidized low-density lipoprotein (oxLDL) has been implicated in the development of atherosclerosis. Follistatin-like protein 1 (FSTL1) play a central role in the inflammation process and modulate cardiovascular disorders. However, little is known about the effects of FSTL1 on the inflammation induced by oxLDL. The aim of this study was to evaluate the anti-inflammatory effect of FSTL1 and investigate potential mechanisms in cultured endothelial cells. A model of oxLDL induced injury in human coronary artery endothelial cells (HCAECs) was established to evaluate the protective role of FSTL1. The mRNA transcription and secretion of TNF-alpha, IL-6, IL-8, ICAM-1, VCAM-1 and MCP-1 were assayed using RT-PCR and ELISA, respectively. We also investigated the effects of FSTL1 on the TLR4/MyD88/NF-kappa B and MAPK signaling pathways. OxLDL increased the expression and release of TLR4, IL-6, IL-8, ICAM-1, VCAM-1 and MCP-1 in a dose and time dependent manner. The effects of oxLDL on the production of inflammatory cytokines by endothelial cells were completely inhibited after depletion of FSTL1. Moreover, down-regulation of FSTL1 resulted in a significant reduction in the expression of TLR4 and its downstream proteins MyD88 and p-p65, along with p-p38, p-JNK and p-ERK. However, FSTL1 had no effect on the JAK/STAT signaling pathway. These findings provide strong evidence that FSTL1 displays anti-inflammatory effects against oxLDL induced pro-inflammatory cytokine production via a mechanism that involves the TLR4/MyD88/NF-kappa B and MAPK signaling pathways. (C) 2016 Elsevier Inc. All rights reserved.