ELMO1 通过 NF-κB 信号通路调节原发性胆汁性胆管炎中巨噬细胞的定向迁移并减轻炎症反应。

ELMO1 regulates macrophage directed migration and attenuates inflammation via NF-κB signaling pathway in primary biliary cholangitis.

机构信息

Clinical Laboratory Department, The Second Affiliated Hospital of Kunming Medical University, Kunming, China, 650101.

出版信息

Dig Liver Dis. 2024 Nov;56(11):1897-1905. doi: 10.1016/j.dld.2024.05.012. Epub 2024 Jun 1.

DOI:10.1016/j.dld.2024.05.012

Abstract

BACKGROUND & AIMS: Primary biliary cholangitis (PBC), a typical autoimmune liver disease, is characterized by an increased infiltration of immune cells. However, the specific molecular mechanisms regulating immune cell migration in PBC are unknown. Engulfment and cell motility 1 (ELMO1) plays an important function in cellular dynamics. In view of this, the aim of this study was to explore the expression of ELMO1 in PBC, its effects on the proliferation, migration, and secretion of inflammatory factors by the mainly regulated immune cells and the specific molecular mechanisms behind it.

METHODS

To determine the expression of ELMO1 in PBC and its major regulatory immune cells in PBC. The migratory and proliferative capacities of ELMO1-deficient macrophages were measured, and their pro-inflammatory cytokine secretion was also detected and explored mechanistically.

RESULTS

ELMO1 expression was up-regulated in the PBC patients and positively correlated with alkaline phosphatase (ALP). ELMO1 mainly regulated macrophages in the liver of PBC patients. Knockdown of ELMO1 did not affect macrophage proliferation, however,knockdown of ELMO1 significantly inhibited macrophage migration,downstream RAC1 activity was diminished, and reduced F-actin synthesis. Knockdown of ELMO1 reduced macrophage inflammatory factor secretion and NF-κB signaling pathway activity was decreased.

CONCLUSIONS

ELMO1 regulates macrophage directed migration and attenuates inflammation via NF-κB signaling pathway in primary biliary cholangitis.

摘要

背景与目的

原发性胆汁性胆管炎（PBC）是一种典型的自身免疫性肝病，其特征为免疫细胞浸润增加。然而，调节 PBC 中免疫细胞迁移的特定分子机制尚不清楚。吞噬和细胞迁移 1（ELMO1）在细胞动力学中发挥重要功能。鉴于此，本研究旨在探讨 ELMO1 在 PBC 中的表达及其对主要调节免疫细胞增殖、迁移和炎症因子分泌的影响及其潜在的分子机制。

方法

检测 PBC 患者中 ELMO1 的表达及其主要调节免疫细胞。测量 ELMO1 缺陷型巨噬细胞的迁移和增殖能力，并检测和探讨其促炎细胞因子的分泌情况及其潜在的分子机制。

结果

ELMO1 在 PBC 患者中表达上调，并与碱性磷酸酶（ALP）呈正相关。ELMO1 主要调节 PBC 患者肝脏中的巨噬细胞。ELMO1 敲低不影响巨噬细胞增殖，但显著抑制巨噬细胞迁移，下游 RAC1 活性降低，F-肌动蛋白合成减少。ELMO1 敲低减少巨噬细胞炎症因子分泌，NF-κB 信号通路活性降低。