Mechanism of Baqi Rougan Formula in Promoting Activation of Th22 Cells and Secretion of IL-22 against Liver Fibrosis
Objective To explore the mechanism of anti-fibrotic action of Baqi Rougan Formula(RGF).Methods Sixty 8-week-old BALB/c mice were randomly assigned to three groups:Control group,Concanavalin A(ConA)model group,and RGF group.Animals model of ConA-induced liver fibrosis were prepared in the model group and RGF group,and the RGF group was then administered with RGF(8.5 g/kg)until the end of the experiment.CD4+T cells and dendritic cells(DCs)were isolated from the peripheral blood of healthy individuals and co-cultured with the human hepatic stellate cell line(LX2)following induction.The expression levels of related genes and proteins were detected.Results Compared to the Control group,the ConA model group exhibited significant increases in serum alanine aminotransferase(ALT),transforming growth factor-beta(TGF-β),hyaluronic acid(HA),interleukin-22(IL-22),interleukin-6(IL-6),tumor necrosis factor-alpha(TNF-α),and interleukin-23(IL-23)levels(P＜0.01,P＜0.05),along with a decrease in albumin(ALB)level(P＜0.01).In contrast,the RGF group showed significant reductions in ALT,TGF-β,HA levels(P＜0.01),and increases in IL-22,IL-6,TNF-α,IL-23 levels compared to the model group(P＜0.01).Histopathological analysis confirmed the protective effect of the RGF against ConA-induced liver fibrosis.When compared to the blank serum group,the RGF-containing serum groups(0.5,1,10 µg/mL)demonstrated elevated mRNA levels of IL-6,TNF-α,IL-23 secreted by DCs(P＜0.01).In the co-culture system,compared to the blank serum group,the RGF-containing serum group exhibited increased IL-22 mRNA and protein expression levels(P＜0.01),and a decrease in alpha-smooth muscle actin(α-SMA)and Collagen Type Ⅰ Alpha 1(Col1 α1)mRNA and protein levels in LX2 cells(P＜0.01).RT-PCR analysis of aging-related inflammatory genes indicated that the RGF-containing serum group could upregulate the expression of matrix metalloproteinase 9(MMP9),IL-6,macrophage inflammatory protein-2(MIP2),p53,and p21 mRNA(P＜0.01),while downregulating the expression of tissue inhibitor of metalloproteinases 1(TIMP1)mRNA(P＜0.01).Conclusions RGF mitigates liver fibrosis by promoting IL-6/TNF-α/IL-23 secretion from DCs,activating Th22 cells,and enhancing IL-22 secretion.This process inhibits the activation of hepatic stellate cells(HSCs)and promotes the senescence of activated HSCs.
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