CCL3 aggravates intestinal damage in NEC by promoting macrophage chemotaxis and M1 macrophage polarization

作者全名："Yuan, Xi; Liu, Wei; Li, Yue; Chen, Kai; Li, Hongdong; Tang, Hong; Yin, Yibing; Song, Zhixin; Chen, Dapeng"

作者地址："[Yuan, Xi; Song, Zhixin; Chen, Dapeng] Childrens Hosp Chongqing Med Univ, Natl Clin Res Ctr Child Hlth & Disorders, Dept Clin Lab, Key Lab Child Dev & Disorders,Chongqing Key Lab Ch, Chongqing, Peoples R China; [Liu, Wei] Chongqing Med Univ, Childrens Hosp, Dept Gastrointestinal & Neonatal Surg, Chongqing, Peoples R China; [Li, Yue] Chongqing Med Univ, Coll Basic Med Sci, Mol Med & Canc Res Ctr, Chongqing, Peoples R China; [Chen, Kai; Yin, Yibing] Chongqing Med Univ, Dept Lab Med, Key Lab Diagnost Med, Chongqing 400016, Peoples R China; [Li, Hongdong] Chongqing Med Univ, Childrens Hosp, Emergency Dept, Chongqing 400016, Peoples R China; [Tang, Hong] Chongqing Med Univ, Affiliated Hosp 1, Dept Crit Care Med, Dept Surg Intens Care Unit, Chongqing, Peoples R China"

通信作者："Song, ZX; Chen, DP (通讯作者)，Childrens Hosp Chongqing Med Univ, Natl Clin Res Ctr Child Hlth & Disorders, Dept Clin Lab, Key Lab Child Dev & Disorders,Chongqing Key Lab Ch, Chongqing, Peoples R China."

来源：PEDIATRIC RESEARCH

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:000903077100002

JCR分区：Q1

影响因子：3.1

年份：2023

卷号：　

期号：　

开始页：　

结束页：　

文献类型：Article; Early Access

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摘要："Background: NEC is a life-threatening gastrointestinal disease in neonates, the pathogenesis of which remains poorly understood. Methods: CCL3 levels in intestinal tissue of mice were measured and analyzed. HE staining was used to assess pathological changes in intestinal tissue. FCM was used to detect the proportion and phenotype of macrophages. RNA-seq and RT-PCR were used to evaluate the effect of CCL3 on macrophages. Results: CCL3 was highly expressed in the intestinal tissues of mice with NEC and induced macrophage infiltration. Transcriptome data showed that CCL3 strongly induced a transition in the phenotype of macrophages into a proinflammatory one. Mechanistically, in vivo experiments confirmed that CCL3 induced M1 macrophage polarization in NEC intestinal tissue, thereby aggravating inflammatory injury of intestinal tissue, which was alleviated by anti-CCL3 treatment. In addition, in vitro experiments showed that CCL3 significantly enhances the expression of M1-related genes in both PM phi and BMDM while inhibiting the expression of M2-related genes, which was also alleviated by anti-CCl3 treatment. Conclusions: Our data elucidated the involvement of CCL3 in the pathogenesis of NEC, in which upregulated CCL3 expression exacerbated inflammatory intestinal damage by regulating macrophage chemotaxis and M1 phenotype polarization, suggesting that blocking CCL3 may be a potential strategy for effective intervention in NEC."

基金机构：National Natural Science Foundation of China; Chongqing Municipal Health Commission [81801956]; Chongqing Science and Technology Commission [2020MSXM050]; Distinguished Young Scholars of the Children's Hospital of Chongqing Medical University [cstc2019jcyj-msxmX0364]

基金资助正文："The study was supported, in part, by the National Natural Science Foundation of China (Grant Number: 81801956 to Z.S.), Chongqing Municipal Health Commission (Grant Number: 2020MSXM050 to D.C.), Chongqing Science and Technology Commission (Grant Number: cstc2019jcyj-msxmX0364 to H.T.), Distinguished Young Scholars of the Children's Hospital of Chongqing Medical University (to Z.S.)"