Baicalin suppresses Th1 and Th17 responses and promotes Treg response to ameliorate sepsis-associated pancreatic injury via the RhoA-ROCK pathway

• Published in: International immunopharmacology 2020-09, Vol.86, p.106685-106685, Article 106685
• Main Authors: Liu, Pingping, Xiao, Zhenghui, Yan, Haipeng, Lu, Xiulan, Zhang, Xinping, Luo, Lan, Long, Caixia, Zhu, Yimin
• Format: Article
• Language: English
• Subjects: Anti-inflammatory agents; Baicalin; Blood; Cecum; Forkhead protein; Foxp3 protein; Helper cells; Homology; Inflammatory diseases; Injury prevention; Interferon; Interleukin 10; Interleukin 17; Kinases; Lymphocytes; Lymphocytes T; Pancreas; Peripheral blood; Receptors; Retinoic acid; Rho-associated kinase; RhoA protein; Rocks; Sepsis; Spleen; Stat3 protein; Stat4 protein; Stat5 protein; Tissues; γ-Interferon
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2020.106685

Recent studies have reported that the imbalance of T helper 1 cell (Th1), Th17 and regulatory T cell (Treg) have been confirmed to play a vital role in the development of sepsis and other inflammatory diseases. Baicalin (BA) has anti-inflammatory properties and improves survival in sepsis. We investigated whether baicalin could regulate Th1, Th17 and Treg responses to ameliorate sepsis-associated pancreatic injury through the ras homolog family member A (RhoA)-Rho kinase (ROCK) pathway. The sepsis model was established by using the cecal ligation and puncture (CLP) method. Fifty mice were randomly divided into five groups (n = 10): sham group, model group, low-dose group (BA-L, 100 mg/kg of baicalin), medium-dose group (BA-M, 200 mg/kg of baicalin) and highdose group (BA-H, 300 mg/kg of baicalin). The effects of baicalin on the pancreatic injury, on changes of Th1, Th17 and Treg cells in vivo and in vitro, on RhoA, ROCK1 and signal transducer and activator of transcription (STAT) signaling pathways, and on levels of interferon-γ (IFN-γ), interleukin-17 (IL-17) and IL-10 were examined. Treatment of the CLP mice with baicalin significantly reduced the extent, scope and severity of the pathological changes of sepsis-associated pancreatic injury. Baicalin evidently reduced Th1 and Th17 cells and increased Treg cells in peripheral blood, spleen, pancreatic tissue and significantly inhibited T-box protein expressed in T cells (T-bet), retinoic acid receptor-related orphan receptor γt (RORγt) and increased forkhead/winged helix transcription factor (Foxp3) expressions in the pancreatic tissue. Baicalin reduced the expressions of RhoA, ROCK1, phosphorylated STAT4 (p-STAT4), p-STAT3 and increased the expression of p-STAT5 in peripheral blood, spleen and pancreatic tissue. Baicalin reduced the expressions of IFN-γ and IL-17 and increased the IL-10 in serum and pancreatic tissue. Baicalin is capable of ameliorating sepsis-associated pancreatic injury and regulating Th1, Th17 and Treg responses in sepsis. The present study provided a potential adjunctive therapy for treating pancreatic injury in sepsis, and further study is needed to reveal its deeper mechanisms.