Abstract
Background Our previous study indicated that Hcy exacerbated DSS-induced colitis by facilitating the differentiation of intestinal T helper cell 17 (Th17), but the precise mechanism remains unidentified. Therefore, our current research aims to elucidate the signaling pathway through which Hcy promotes the differentiation of Th17 cells.
Methods BALb/c mice were randomly assigned into six groups. The model of mice colitis was induced using 3% DSS, while the model of Hyperhomocysteinaemia was induced using 1.7% methionine. The concentrations of Hcy and prostaglandin E2 (PGE2) were measured using enzyme linked immunosorbent assay (ELISA). The protein expressions of cytosolic phospholipase A2 (cPLA2), phosphorylated-cPLA2 (p-cPLA2), cyclooxygenase 2 (COX2), cyclic adenosine monophosphate (cAMP), signal transducer and activator of transcription 3 (STAT3), phosphorylated-STAT3 (p-STAT3), interleukin 17A (IL-17A) and retinoid-related orphan nuclear receptor-γt (RORγt) were assessed using western blot analysis.
Results Compared to the DSS+HHcy group, the addition of the COX inhibitor did not significantly alter the protein expression of p-PLA2/PLA2, but led to significant decreases in serum PGE2 concentration, cAMP and p-STAT3/STAT3 protein expression. The protein expressions of p-PLA2/PLA2, COX2, and cAMP upstream of STAT3 inhibitor addition did not exhibit significant changes. However, PGE2 concentration and p-STAT3/STAT3 protein expression were notably reduced. After the COX inhibitor and STAT3 inhibitor added, the protein expression of IL-17A and RORγt and the levels of IL-17A and IL-23R in CD4+T cells were significantly reduced.
Conclusion HHcy aggravated DSS-induced colitis by promoting the differentiation and proliferation of Th17 cells through the PGE2 / STAT3 signaling pathway.