黏蛋白 1 对于柯萨奇病毒 B3 诱导的胰腺炎炎症反应是必需的。

Mucin-1 is required for Coxsackie Virus B3-induced inflammation in pancreatitis.

机构信息

Division of Surgical Oncology, Department of Surgery, Fred and Pamela Buffet Cancer Center, University of Nebraska Medical Center, Omaha, NE, USA.

Department of Internal Medicine, Division of Gastroenterology and Hepatology, University of Nebraska Medical Center, Omaha, NE, USA.

出版信息

Sci Rep. 2019 Jul 23;9(1):10656. doi: 10.1038/s41598-019-46933-y.

DOI:10.1038/s41598-019-46933-y

PMID:31337812

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6650496/

Abstract

The Muc-1 oncoprotein is a tumor-associated mucin often overexpressed in pancreatic cancer. We report that knockout of Muc-1 reduced the degree of pancreatic inflammation that resulted from infection with Coxsackievirus B3 (CVB3) in a mouse model. CVB3-infected Muc-1-deficient (Muc-1) mice had significantly reduced infiltration of macrophages into the murine pancreas. We found that Muc-1 signaling through NF-κB increased expression of ICAM-1, a pro-inflammatory mediator that recruits macrophages. Further investigation revealed that bone marrow derived macrophages (BMDM) from the Muc-1 mice exhibited defective migration properties, in part due to low expression of the C-C motif chemokine receptor (CCR2) and the integrin Very Late Antigen 4 (VLA-4). The results presented here provide novel insight into the role of Muc-1 in regulating the inflammatory response and the cellular microenvironment in pancreatitis.

摘要

黏蛋白 1 癌蛋白是一种肿瘤相关黏蛋白，在胰腺癌中常过表达。我们的报告显示，在一种小鼠模型中，敲除黏蛋白 1 可减少柯萨奇病毒 B3（CVB3）感染引起的胰腺炎症程度。CVB3 感染的黏蛋白 1 缺陷型（Muc-1）小鼠的巨噬细胞浸润到胰腺中的程度显著降低。我们发现黏蛋白 1 通过 NF-κB 信号转导增加了细胞间黏附分子 1（ICAM-1）的表达，ICAM-1 是一种募集巨噬细胞的促炎介质。进一步的研究表明，来自 Muc-1 小鼠的骨髓来源的巨噬细胞（BMDM）表现出迁移功能缺陷，部分原因是 C-C 基序趋化因子受体（CCR2）和整合素 Very Late Antigen 4（VLA-4）的低表达。这里呈现的结果为黏蛋白 1 在调节胰腺炎中的炎症反应和细胞微环境中的作用提供了新的见解。