GFI-1 Protects Against Lipopolysaccharide-Induced Inflammatory Responses and Apoptosis by Inhibition of the NF-κB/TNF-α Pathway in H9c2 Cells.

Abstract

Growth factor independence 1 (Gfi-1) has been widely studied for its anti-inflammatory and anti-apoptotic effects. However, whether Gfi-1 has similar effects on H9c2 cardiomyocytes has not yet been reported. In this study, we explored the effect of Gfi-1 on lipopolysaccharide (LPS)-induced inflammatory responses and apoptosis in H9c2 cells. We found that LPS induced the increased expression of TNF-α and IL-6 in the LPS group. After transfection of the Gfi-1 overexpression plasmid, the expression of TNF-α and IL-6 decreased significantly in the LPS + Gfi-1 group. Gfi-1 clearly blocked LPS-induced NF-κB, TNF-α, TNFR1, cleaved-caspase-3 and cleaved-caspase-8 expression and increased Gfi-1 and Bcl-xL expression in H9c2 cells. Similarly, compared with the LPS group, Gfi-1 significantly decreased the expression of cleaved-caspase3/8 and increased the expression of Bcl-xL in the LPS + Gfi-1 group, as verified by immunocytochemical analysis. Furthermore, Gfi-1 markedly inhibited LPS-induced H9c2 cardiomyocyte apoptosis in the LPS + Gfi-1 group, as determined by TEM, TUNEL and flow cytometry. Taken together, these results demonstrate that Gfi-1 may have protective effects against LPS-induced inflammatory responses and apoptosis in H9c2 cells. Gfi-1 may be a novel molecule for treating septic cardiomyopathy.