Inhibition of COX-2 ameliorates murine liver schistosomiasis japonica through splenic cellular immunoregulation
2022
Qi, Zhang | Lan, Chen | Xiaofang, Ji | Juanjuan, Tang | Zheng, Fu | Ding, Huang | Erxia, Shen | Zi, Li
BACKGROUND: We have reported the positive association of the cyclooxygenase 2 (COX-2)/prostaglandin E2 (PGE2) axis with liver fibrosis induced by Schistosoma japonicum (Sj) infection, and TLR4 signaling controlled this axis. However, how COX-2 regulates immune response during Sj infection is still unclear. METHODS: Hematoxylin and eosin staining was used to evaluate the effect of the COX-2-specific inhibitor NS398 on liver granulomatous inflammation and fibrosis. Flow cytometry was used to explore the frequency and amount of different immune cell infiltration in the spleen during Sj infection. RESULTS: NS398 significantly reduced the size of liver granuloma, spleen, and mesenteric lymph node (MLN) and alleviated chronic granulomatous inflammation. Mechanically, this might be by decreasing the number of Sj-induced macrophages and T helper type 1 (Th1), Th2, T follicular helper (Tfh), T follicular regulatory (Tfr), and germinal center B (GC B) cells. There were no differences in the number of neutrophils, myeloid-derived suppressor cells, Th17 cells, regulatory T cells (Treg), or total B cells in the spleen of the mice with or without NS398 treatment. CONCLUSIONS: COX-2/PGE2 inhibition may represent a potential therapeutic approach for schistosomiasis japonica through splenic cellular immunoregulation.
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