Effect of Coronin-1 on macrophage polarization by regulating the expression of CD14

Xiaoxia FAN; Quan CHEN; Xuehua SUN; Ruoyuan TIAN

doi:10.16016/j.1000-5404.202104087

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Effect of Coronin-1 on macrophage polarization by regulating the expression of CD14

Basic Medicine | 更新时间：2026-01-09

- Effect of Coronin-1 on macrophage polarization by regulating the expression of CD14
- Journal of Third Military Medical University Vol. 43, Issue 19, Pages: 1884-1893(2021)
- 作者机构：
  
  400016 重庆，重庆医科大学基础医学院免疫学教研室
- 作者简介：
- 基金信息：
- DOI：10.16016/j.1000-5404.202104087
  CLC： R341;R392.12;R392.2
- Received：14 April 2021，
  
  Revised：2021-06-07，
  
  Published：15 October 2021
- 稿件说明：
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Xiaoxia FAN, Quan CHEN, Xuehua SUN, et al. Effect of Coronin-1 on macrophage polarization by regulating the expression of CD14[J]. Journal of Third Military Medical University, 2021, 43(19): 1884-1893.
DOI：

Xiaoxia FAN, Quan CHEN, Xuehua SUN, et al. Effect of Coronin-1 on macrophage polarization by regulating the expression of CD14[J]. Journal of Third Military Medical University, 2021, 43(19): 1884-1893. DOI： 10.16016/j.1000-5404.202104087.

摘要

目的

探讨冠蛋白-1(Coronin-1)与巨噬细胞极化的相关性及可能机制。

方法

建立M1、M2型RAW264.7鼠巨噬细胞模型，通过Real-time PCR和Western blot检测Coronin-1的表达；构建过表达(Coronin-1 Plus)、敲除(Coronin-1 KO)细胞系，通过Real-time PCR和Western blot检测过表达、敲除和正常表达Coronin-1细胞组的一氧化氮合酶(inducible nitric oxide synthase

iNOS)水平；利用蛋白质互作网络(PPI)和GO分析Coronin-1和CD14相关蛋白的互作与富集，再通过Real-time PCR和Western blot检测过表达、敲除和正常表达Coronin-1细胞组的CD14水平以及经脂多糖(lipopolysaccharide

LPS，100 ng/mL)处理后的iNOS水平；构建CD14敲减的细胞系(Control-CD14 KD)、CD14敲减的Coronin-1 Plus细胞系(Coronin-1 Plus-CD14 KD)，经LPS (100 ng/mL)处理后，通过Real-time PCR和Western blot检测iNOS的表达。

结果

成功构建M1、M2型巨噬细胞模型，M1型Coronin-1表达显著高于对照组(

0.05)；Coronin-1 Plus组iNOS mRNA的表达显著低于对照组(

0.01)，Coronin-1 Plus组CD14的表达显著高于对照组(

0.05)；经LPS处理后，Coronin-1 Plus组iNOS的表达显著高于对照组(

0.01)；经LPS处理的Control-CD14 KD、Coronin-1 Plus-CD14 KD组细胞的iNOS水平与对照组比较，差异无统计学意义。

结论

巨噬细胞向M1型极化导致了Coronin-1的高表达，而Coronin-1过表达并不能直接导致细胞向M1型极化，但Coronin-1过表达可导致CD14表达上调，Coronin-1可通过CD14途径促进LPS诱导巨噬细胞向M1型极化。

Abstract

Objective

To investigate the correlation between Coronin-1 and macrophage polarization and its possible mechanism.

Methods

Firstly

M1 and M2 RAW246.7 macrophage cells were established

and the expression of Coronin-1 at mRNA and protein level was detected by real-time PCR and Western blotting. Then

over-expressed (Coronin-1 Plus) and knockout (Coronin-1 KO) cell lines were constructed in RAW246.7 cells

and the expression levels of inducible nitric oxide synthase (iNOS) in over-expressed

knockout and normal-expressed Coronin-1 cells were detected by real-time PCR and Western blotting. The interaction and enrichment of Coronin-1 and CD14 related proteins were analyzed by protein-protein interaction (PPI) network and Gene Ontology (GO) enrichment analysis. Real-time PCR and Western blotting were used to detect the expression level of CD14 in over-expressed

knockout and normal Coronin-1 cells

and the expression level of iNOS after treatment with 100 ng/mL LPS. Then

CD14 knockdown cell lines (Control-CD14 KD) and CD14 knockdown Coronin-1 Plus cell lines (Coronin-1 Plus-CD14 KD) were constructed. After treatment with LPS (100 ng/mL)

the expression of iNOS was detected by real-time PCR and Western blotting.

Results

M1 and M2 macrophage models were successfully constructed

and the expression of Coronin-1 in M1 type macrophages was significantly higher than that in the Control group (

0.05). The mRNA expression of iNOS was significantly lower in Coronin-1 Plus group than control group (

0.01)

and the expression of CD14 was obviously higher in Coronin-1 Plus group than Control group (

0.05). After LPS treatment

the expression of iNOS in Coronin-1 Plus group was significantly higher than that in Control group (

0.01). There was no significant difference in iNOS level of the LPS treated Control-CD14 KD and Coronin-1 Plus-CD14 KD groups with the Control group (

0.05).

Conclusion

The M1 polarization of macrophages leads to higher expression of Coronin-1

but the over-expression of Coronin-1 does not directly lead to the M1 polarization of macrophages. Its over-expression can lead to up-regulation of CD14 expression

and Coronin-1 can promote LPS-induced macrophages to M1 type polarization through the CD14 pathway.

关键词

Keywords

references

MUELLER P, MASSNER J, JAYACHANDRAN R, et al . Regulation of T cell survival through coronin-1-mediated generation of inositol-1, 4, 5-trisphosphate and calcium mobilization after T cell receptor triggering[J ] . Nat Immunol, 2008, 9(4): 424-431. DOI:10.1038/ni1570.

PICK R, BEGANDT D, STOCKER T J, et al . Coronin 1A, a novel player in integrin biology, controls neutrophil trafficking in innate immunity[J ] . Blood, 2017, 130(7): 847-858. DOI:10.1182/blood-2016-11-749622.

HARALDSSON M K, LOUIS-DIT-SULLY C A, LAWSON B R, et al . The lupus-related Lmb3 locus contains a disease-suppressing Coronin-1A gene mutation[J ] . Immunity, 2008, 28(1): 40-51. DOI:10.1016/j.immuni.2007.11.023.

KAMINSKI S, HERMANN-KLEITER N, MEISEL M, et al . Coronin 1A is an essential regulator of the TGFβ receptor/SMAD3 signaling pathway in Th17 CD4 + T cells[J ] . J Autoimmun, 2011, 37(3): 198-208. DOI:10.1016/j.jaut.2011.05.018..

FERRARI G, LANGEN H, NAITO M, et al . A coat protein on phagosomes involved in the intracellular survival of Mycobacteria[J ] . Cell, 1999, 97(4): 435-447. DOI:10.1016/s0092-8674(00)80754-0.

SCHMIEDER A, MICHEL J, SCHÖNHAAR K, et al . Differentiation and gene expression profile of tumor-associated macrophages[J ] . Semin Cancer Biol, 2012, 22(4): 289-297. DOI:10.1016/j.semcancer.2012.02.002.

CHEN J J W, LIN Y C, YAO P L, et al . Tumor-associated macrophages: the double-edged sword in cancer progression[J ] . J Clin Oncol, 2005, 23(5): 953-964. DOI:10.1200/jco.2005.12.172.

OH H, PARK S H, KANG M K, et al . Asaronic acid attenuates macrophage activation toward M1 phenotype through inhibition of NF-κB pathway and JAK-STAT signaling in glucose-loaded murine macrophages[J ] . J Agric Food Chem, 2019, 67(36): 10069-10078. DOI:10.1021/acs.jafc.9b03926.

TANIGAWA K, SUZUKI K, KIMURA H, et al . Tryptophan aspartate-containing coat protein (CORO1A) suppresses Toll-like receptor signalling in Mycobacterium leprae infection[J ] . Clin Exp Immunol, 2009, 156(3): 495-501. DOI:10.1111/j.1365-2249.2009.03930.x.

周静瑶, 陈全, 周芳妮, 等. 冠蛋白-1不同表达水平对巨噬细胞iNOS、TLRs表达以及凋亡的影响[J]. 中国细胞生物学学报, 2017, 39(2): 148-156. DOI:10.11844/cjcb.2017.02.0271.

ZHOU J Y, CHEN Q, ZHOU F N, et al . The effects of coronin-1 with different expression levels on iNOS and TLRs expression and apoptosis in RAW264.7 cells[J ] . Chin J Cell Biol, 2017, 39(2): 148-156. DOI:10.11844/cjcb. 2017.02.0271.

PŁÓCIENNIKOWSKA A, HROMADA-JUDYCKA A, BORZECKA K, et al . Co-operation of TLR4 and raft proteins in LPS-inducedpro-inflammatory signaling[J ] . Cell Mol Life Sci, 2015, 72(3): 557-581. DOI:10.1007/s00018- 014-1762-5.

EDWARDS J P, ZHANG X, FRAUWIRTH K A, et al . Biochemical and functional characterization of three activated macrophage populations[J ] . J Leukoc Biol, 2006, 80(6): 1298-1307. DOI:10.1189/jlb.0406249.

WARDE-FARLEY D, DONALDSON S L, COMES O, et al . The GeneMANIA prediction server: biological network integration for gene prioritization and predicting gene function[J ] . Nucleic Acids Res, 2010, 38(web server issue): W214-W220. DOI:10.1093/nar/gkq537.

ITALIANI P, BORASCHI D. From monocytes to M1/M2 macrophages: phenotypical vs . functional differentiation[J ] . Front Immunol, 2014, 5: 514. DOI:10.3389/fimmu. 2014.00514.

MANTOVANI A, SOZZANI S, LOCATI M, et al . Macrophage polarization: tumor-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes[J ] . Trends Immunol, 2002, 23(11): 549-555. DOI:10.1016/s1471-4906(02)02302-5.

UETRECHT A C, BEAR J E. Coronins: the return of the crown[J]. Trends Cell Biol, 2006, 16(8): 421-426. DOI:10.1016/j.tcb.2006.06.002.

GATFIELD J, ALBRECHT I, ZANOLARI B, et al . Association of the leukocyte plasma membrane with the actin cytoskeleton through coiled coil-mediated trimeric coronin 1 molecules[J ] . Mol Biol Cell, 2005, 16(6): 2786-2798. DOI:10.1091/mbc.e05-01-0042.

JAYACHANDRAN R, SUNDARAMURTHY V, COMBA-LUZIER B, et al . Survival of Mycobacteria in macrophages is mediated by coronin 1-dependent activation of calcineurin[J ] . Cell, 2007, 130(1): 37-50. DOI:10.1016/j.cell.2007.04.043.

CIESIELSKA A, MATYJEK M, KWIATKOWSKA K. TLR4 and CD14 trafficking and its influence on LPS-induced pro-inflammatory signaling[J]. Cell Mol Life Sci, 2021, 78(4): 1233-1261. DOI:10.1007/s00018-020-03656-y.

FU Y J, XU B, HUANG S W, et al . Baicalin prevents LPS-induced activation of TLR4/NF-κB p65 pathway and inflammation in mice via inhibiting the expression of CD14[J ] . Acta Pharmacol Sin, 2021, 42(1): 88-96. DOI:10.1038/s41401-020-0411-9..

ESPARZA G A, TEGHANEMT A, ZHANG D, et al . Endotoxin{middle dot}albumin complexes transfer endotoxin monomers to MD-2 resulting in activation of TLR4[J ] . Innate Immun, 2012, 18(3): 478-491. DOI:10.1177/1753425911422723.

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