IL-6 induced lncRNA MALAT1 enhances TNF-α expression in LPS-induced septic cardiomyocytes via activation of SAA3.

Y-T Zhuang, D-Y Xu, G-Y Wang, J-L Sun, Y Huang, S-Z Wang

European review for medical and pharmacological sciences 2017 Jan

filter terms:

This study aimed to explore the expression of MALAT1 and its correlation with TNF-α production in lipopolysaccharide (LPS)-induced septic cardiomyocytes. Then, the effect of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) on LPS-induced cardiomyocyte apoptosis is further studied. The hub genes in cell response to LPS treatments was analyzed by using Affymetrix gene profiling data downloaded from GEO dataset (GSE3140). Mice model of sepsis was induced by intraperitoneal injection of LPS. HL-1 cells were used as the in vitro cell model. MALAT1 and serum amyloid antigen 3 (SAA3) expression were measured by the qRT-PCR analysis. IL-6, TNF-α, and SAA3 concentrations were quantified by the ELISA assay. Flow cytometric analysis and TUNEL assay were performed to detect cell apoptosis. IL-6 is a hub gene in cell response to LPS treatment and induces MALAT1 upregulation in cardiomyocytes. MALAT1 siRNA had an inhibitive effect, while MALAT1 overexpression showed enhancing effect on LPS induced TNF-α elevation. HL-1 cells treated with LPS had significantly elevated SAA3 expression. Inhibition of SAA during LPS treatment significantly reduced the TNF-α expression, while the addition of apo SAA significantly abrogated the suppressive effect of MALAT1 siRNA on TNF-α expression. HL-1 cells transfected with MALAT1 siRNA were less susceptible to LPS-induced cell apoptosis and with a lower apoptosis rate than the control group. IL-6 induced MALAT1 upregulation in cardiomyocytes in response to LPS treatment. MALAT1 can enhance TNF-α expression at least partly via SAA3 in LPS-treated cardiomyocytes. MALAT1 upregulation is a mechanism of cardiomyocyte death in response to the LPS stimulation.

Citation

Y-T Zhuang, D-Y Xu, G-Y Wang, J-L Sun, Y Huang, S-Z Wang. IL-6 induced lncRNA MALAT1 enhances TNF-α expression in LPS-induced septic cardiomyocytes via activation of SAA3. European review for medical and pharmacological sciences. 2017 Jan;21(2):302-309