Abstract:

Objective To investigate the role and mechanism of Rho-related GTP-binding protein F （RhoF）-mediated Th17 polarization in the development of severe acute pancreatitis （SAP）. Methods RhoF transgenic mice were randomly divided into control group （n = 10）， SAP group （n = 10） and SAP+Y-27632 group （n = 10）， and WT mice were randomly divided into control group （n = 10）， SAP group （n = 10） and SAP+Y-27632 group （n = 10）. SAP models were established in all groups except the control group. The SAP+Y-27632 group was infused with Y-27632 via tail vein after model establishment. T cells in mouse blood samples were isolated for RhoF， p-MYPT1 protein detection and ROCK activity determination， and the percentage of lymphoid CD4⁺T cells producing IL-17 was analyzed by flow cytometry. Results The expression of RhoF and p-MYPT1 was increased in T cells in the SAP group compared with that in the control group （P < 0.01）， and the level of RhoF was closely correlated with that of p-MYPT1 （P = 0.018）. The expression of RhoF protein level in T cells of mice in the RhoF group increased by approximately 30% compared to that in the WT group， and the level of spontaneous IL-17 production by CD4⁺ T cells was significantly increased （P = 0.003）. Compared with WT mice， the histological score of pancreatic injury， the expression of RhoF and p-MYPT1 in T cells， the number of IL-17⁺ T cells and serum IL-17 level in RhoF transgenic mice were significantly increased （P < 0.05）. The histological score， RhoF and p-MYPT1 expression of T cells， IL-17⁺ T cell numbers and serum IL-17 level were significantly lower in the SAP+Y-27632 group than those in the SAP group （P < 0.05）. Conclusion RhoF/ROCK signaling pathway-mediated polarization of Th17 cells is involved in the pathogenesis of SAP.

Key words: Rho-associated GTP-binding protein F, Th17 cells, severe acute pancreatitis