TLR4/AP-1-Targeted Anti-Inflammatory Intervention Attenuates Insulin Sensitivity and Liver Steatosis
AP-1 siRNA transfection extenuated PA-induced inflammation in RAW264.7 cells and metabolic disorders in cocultured AML hepatocytes. AP1 siRNA transfection significantly diminished PA-induced elevation of the AP1 expression in RAW264.7 cells (a–e). AP1 siRNA transfection seemed to exacerbate the increases of the TLR4 expression in these cells (f–h). AP1 siRNA transfection diminished the DNA binding activity of AP1, but it seemed not be able to meliorate PA-induced increases in the CD11c mRNA expression or decreases in the CD206 mRNA expression (i, j). AP1 siRNA transfection was not able to palliate PA-induced augmentation in JNK phosphorylation (k), as well as in the mRNA expression and DNA binding activity of NF-κB (l, m). AP1 siRNA transfection alleviated the increases in proinflammatory factor (IL-1β, IL-6, and TNF-α) expression in RAW264.7 macrophages and TNF-α and IL-6 levels in the supernatant (n, o) and attenuated PA-induced decreases in the IL-10 expression (n). AP1 siRNA transfection in RAW264.7 macrophages significantly moderated the decreases in AKT phosphorylation level and lipid accumulation in cocultured AML12 hepatocytes (p–r). Data are presented as ; and compared with the NC group; & and && compared with the Scramble-pLV group (d, n, o, q); # and ## compared with the PA group (e, j, n, o, q).
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