抑制 COX-2 可通过脾细胞免疫调节改善日本血吸虫病肝纤维化。

Inhibition of COX-2 ameliorates murine liver schistosomiasis japonica through splenic cellular immunoregulation.

机构信息

Sino‑French Hoffmann Institute, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, 511436, Guangdong Province, China.

Immunology Department, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, 511436, Guangdong Province, China.

出版信息

Parasit Vectors. 2022 Apr 23;15(1):144. doi: 10.1186/s13071-022-05201-1.

DOI:10.1186/s13071-022-05201-1

PMID:35461268

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9034617/

Abstract

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.

摘要

背景

我们曾报道环氧化酶 2（COX-2）/前列腺素 E2（PGE2）轴与日本血吸虫（Sj）感染诱导的肝纤维化之间存在正相关，TLR4 信号通路控制该轴。然而，COX-2 如何在 Sj 感染过程中调节免疫反应尚不清楚。

方法

苏木精和伊红染色用于评估 COX-2 特异性抑制剂 NS398 对肝肉芽肿炎症和纤维化的影响。流式细胞术用于探索 Sj 感染过程中脾脏中不同免疫细胞浸润的频率和数量。

结果

NS398 显著减小了肝肉芽肿、脾脏和肠系膜淋巴结（MLN）的大小，并缓解了慢性肉芽肿炎症。其机制可能是通过减少 Sj 诱导的巨噬细胞和辅助性 T 细胞 1（Th1）、Th2、滤泡辅助性 T 细胞（Tfh）、滤泡调节性 T 细胞（Tfr）和生发中心 B 细胞的数量。在有无 NS398 治疗的小鼠脾脏中，中性粒细胞、髓源抑制细胞、Th17 细胞、调节性 T 细胞（Treg）或总 B 细胞的数量均无差异。