Activin suppresses the inflammatory response of TNF-α-stimulated human umbilical vein endothelial cells

Activins belong to the transforming growth factor (TGF)-13 superfamily and are involved in the regulation of homeostasis, proliferation, differentiation, and inflammation. In the present study, we examined the mechanism by which activin regulates the transcription of tumor necrosis factor-?? (TNF-??)-stimulated cytokines, chemokines, toll-like receptors (TLRs), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) in human umbilical vein endothelial cells (HUVECs), and the involvement of the nuclear factor-KB (NF-KB) and mitogen-activated protein kinase (MAPK) signaling pathways. Cell viability was analyzed using MTS/PES solution, mRNA expression was measured by reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and protein expression was measured by immunoblotting. TNF-?? increased the mRNA expression of cytokines (IL-113 and IL-6), chemokines (IL-8 and MCP-1), and TLR2, as well as the mRNA and protein expression of iNOS and COX-2. Activin decreased TNF-??-induced cytokine, chemokine, and TLR mRNA expression as well as TNF-??-in-duced iNOS and COX-2 mRNA and protein expression. In addition, activin suppressed the phosphorylation of NF-KB p65 in TNF-??-stimulated HUVECs and reduced TNF-??-induced phosphorylation of AKT, JNK, ERK, and p38 MAPK. Our results demonstrate that the anti-inflammatory effects of activin are mediated by inflammatory response genes through the inhibition of NF-KB and AKT/JNK/MAPK signaling.

Automated summary

In this study, it was found that activin exerts anti-inflammatory effects by inhibiting the inflammatory response genes in the NF-KB and AKT/JNK/MAPK signaling pathways.