High-mobility group box 1 protein (HMGB1) in maternal plasma affects Th17/Treg balance via receptor for advanced glycation end products( RAGE) -IL-6 pathway in preeclamptic pregnancies / 中华微生物学和免疫学杂志

ABSTRACT

Objective To analyze the relationships of high mobility group box 1 protein (HMGB1) with regulatory T cells (Treg), T helper 17 cells (Th17) and cytokine secrtion in peripheral blood of gravidas with preeclampsia(PE),and to investigate the mechanism of HMGB1 in regulating Th17/Treg ratio via receptor for advanced glycation end products (RAGE)-IL-6 pathway. Methods Forty gravi-das with mild(20 cases) and severe(20 cases) PE were recruited as experimental groups,20 heathy gravi-das in the third trimester of pregnancy were enrolled as control group. Concentrations of HMGB1,IL-6,IL-17 and TGF-β in peripheral blood of all subjects were determined by enzyme-linked immunosorbent assay (ELISA). Real-time quantitative PCR(RT-PCR) was used to detect the expression of RAGE at mRNA lev-el in peripheral blood mononuclear cells(PBMCs). The percentages of Treg and Th17 cells were determined by flow cytometry. RT-PCR was performed to analyze changes in the expression of RAGE,IL-6,Foxp3 and RORγt at mRNA level after the PBMCs isolated from 20 garvidas with PE were cultured in vitro and stimula-ted with recombinant human HMGB1 (rhHMGB1). Results The levels of HMGB1,IL-6,Th17 and IL-17 in peripheral blood of gravidas with PE were significantly higher than those in the normal pregnancy group. Moreover,HMGB1 level was positively correlated with IL-6 level and ratios of Th17/Treg and IL-17/TGF-β in preeclamptic pregancies. In vitro stimulation of PBMCs with rhHMGB1 significantly enhanced the expres-sion of RAGE,IL-6 and RORγt at mRNA level, but suppressed the expression of Foxp3 at mRNA level. Conclusion Enriched HMGB1 in plasma shifts the Th17/Treg balance towards Th17 dominance via the RAGE-IL-6 pathway, which exacerbates inflammation and participates in the onset of preeclampsia during pregnancy.