Effect of Baicalin on the LPS-Induced Production of Inflammatory Mediators in Low-Dose Corticosterone Pretreated RAW 267.4 cells and Hepa1c1c-7 Cells

Abstract

Low-dose glucocorticoids (GCs) are known to induce inflammation and immunosuppression. However, whether preconditioning with a low dose of GCs induces hepatic inflammation remains unclear. Although baicalin has beneficial therapeutic activity against liver damage, 100 μM baicalin enhances the lipopolysaccharide (LPS)-induced production of inflammatory acute-phase proteins in Hepa1c1c-7 cells. This study was performed to investigate the effect of 100 μM baicalin on the LPS-induced production of inflammatory mediators in liver cells, including Kupffer cells and hepatocytes, pre-conditioned with a low dose of GCs. RAW 267.4 cells and Hepa1c1c-7 cells were pretreated with 50 (cort 50) or 100 ng/mL (cort 100) corticosterone for 24 h and then cultured with 100 μM baicalin in fresh complete medium in the presence of LPS. Our results demonstrated that baicalin markedly decreased the LPS-induced production of TNF-α, IL-6, IL-1β, and nitric oxide in RAW 267.4 cells. Baicalin also strongly attenuated the LPS-induced production of TNF-α in cort 50- and cort 100-pretreated RAW 267.4 cells. Baicalin significantly upregulated the production of IL-6 induced by LPS and the production of VEGF decreased by LPS, but decreased the LPS-induced production of CRP in cort 100- pretreated Hepa1c1c-7 cells compared to untreated Hepa1c1c-7 cells. In conclusion, these findings suggest that 100 μM baicalin may enhance the LPS-induced production of inflammatory acute-phase proteins in hepatocytes, whereas it may downregulate these protein levels in macrophages and Kupffer cells. Moreover, preconditioning with a low dose of corticosterone may prime the effects of 100 μM baicalin on the LPS-induced production of IL-6 in hepatocytes, leading to hepatic insulin resistance or fatty liver disease.