Cargando…

Progranulin inhibits LPS-induced macrophage M1 polarization via NF-кB and MAPK pathways

BACKGROUND: Macrophage M1 polarization plays a pivotal role in inflammatory diseases. Progranulin (PGRN) has potential anti-inflammation action, however, the effect of PGRN on macrophage M1 polarization has been poorly studied. Our study aimed to investigate the effect of PGRN on lipopolysaccharide...

Descripción completa

Detalles Bibliográficos
Autores principales: Liu, Lianlian, Guo, Hongmei, Song, Aimei, Huang, Jiahui, Zhang, Yu, Jin, Shanshan, Li, Shutong, Zhang, Liguo, Yang, Chengzhe, Yang, Pishan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7275413/
https://www.ncbi.nlm.nih.gov/pubmed/32503416
http://dx.doi.org/10.1186/s12865-020-00355-y
_version_ 1783542777839091712
author Liu, Lianlian
Guo, Hongmei
Song, Aimei
Huang, Jiahui
Zhang, Yu
Jin, Shanshan
Li, Shutong
Zhang, Liguo
Yang, Chengzhe
Yang, Pishan
author_facet Liu, Lianlian
Guo, Hongmei
Song, Aimei
Huang, Jiahui
Zhang, Yu
Jin, Shanshan
Li, Shutong
Zhang, Liguo
Yang, Chengzhe
Yang, Pishan
author_sort Liu, Lianlian
collection PubMed
description BACKGROUND: Macrophage M1 polarization plays a pivotal role in inflammatory diseases. Progranulin (PGRN) has potential anti-inflammation action, however, the effect of PGRN on macrophage M1 polarization has been poorly studied. Our study aimed to investigate the effect of PGRN on lipopolysaccharide (LPS)-induced macrophage M1 polarization and clarify the underlying mechanisms. METHODS: RAW264.7 cells were polarized to M1 macrophage by LPS with or without recombinant PGRN (rPGRN) and tumor necrosis factor alpha antibody (anti-TNF-α). A cell counting kit-8 assay (CCK-8), flow cytometry, Quantitative Real-Time PCR assay (q-PCR), Western blot assay and enzyme-linked immunosorbent assay (ELISA) were used to determine the effect of different treatments on cell proliferation, expression of surface phenotype marker and expressions and secretion of inflammatory cytokines. The activation of NF-κB/mitogen-activated protein kinase (MAPK) pathways and the nuclear translocation of NF-κB p65 were detected by Western blot and immunofluorescence respectively. THP-1 and primary bone marrow-derived monocytes (BMDMs) were also used to demonstrate effect of PGRN on expressions and secretion of inflammatory cytokines induced by LPS. RESULTS: In RAW264.7 cells, rPGRN at concentrations below 80 ng/ml significantly promoted cell proliferation in dose dependent fashion. rPGRN significantly inhibited LPS-induced change of phenotype (CD86/CD206 ratio) and function (tumor necrosis factor (TNF-α) and inducible nitric oxide synthase (iNOS) expressions). LPS-stimulated secretion of TNF-α and activated phosphorylation of IKKα/β, IкBα, p65, JNK and p38 and the nucleus translocation of NF-кB p65 were also significantly downregulated by rPGRN. In addition, recombinant TNF-α (rTNF-α) significantly boosted TNF-α and iNOS expression vs the control group. Moreover, anti-TNF-α significantly inhibited LPS-induced TNF-α and iNOS expression. In THP-1 and BMDM cells, reversing effect of rPGRN on LPS-enhanced expressions of TNF-α and iNOS and secretion of TNF-α was further demonstrated. CONCLUSIONS: PGRN down-regulates LPS-induced macrophage M1 polarization in phenotype and function via NF-κB/MAPK signaling pathways.
format Online
Article
Text
id pubmed-7275413
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-72754132020-06-08 Progranulin inhibits LPS-induced macrophage M1 polarization via NF-кB and MAPK pathways Liu, Lianlian Guo, Hongmei Song, Aimei Huang, Jiahui Zhang, Yu Jin, Shanshan Li, Shutong Zhang, Liguo Yang, Chengzhe Yang, Pishan BMC Immunol Research Article BACKGROUND: Macrophage M1 polarization plays a pivotal role in inflammatory diseases. Progranulin (PGRN) has potential anti-inflammation action, however, the effect of PGRN on macrophage M1 polarization has been poorly studied. Our study aimed to investigate the effect of PGRN on lipopolysaccharide (LPS)-induced macrophage M1 polarization and clarify the underlying mechanisms. METHODS: RAW264.7 cells were polarized to M1 macrophage by LPS with or without recombinant PGRN (rPGRN) and tumor necrosis factor alpha antibody (anti-TNF-α). A cell counting kit-8 assay (CCK-8), flow cytometry, Quantitative Real-Time PCR assay (q-PCR), Western blot assay and enzyme-linked immunosorbent assay (ELISA) were used to determine the effect of different treatments on cell proliferation, expression of surface phenotype marker and expressions and secretion of inflammatory cytokines. The activation of NF-κB/mitogen-activated protein kinase (MAPK) pathways and the nuclear translocation of NF-κB p65 were detected by Western blot and immunofluorescence respectively. THP-1 and primary bone marrow-derived monocytes (BMDMs) were also used to demonstrate effect of PGRN on expressions and secretion of inflammatory cytokines induced by LPS. RESULTS: In RAW264.7 cells, rPGRN at concentrations below 80 ng/ml significantly promoted cell proliferation in dose dependent fashion. rPGRN significantly inhibited LPS-induced change of phenotype (CD86/CD206 ratio) and function (tumor necrosis factor (TNF-α) and inducible nitric oxide synthase (iNOS) expressions). LPS-stimulated secretion of TNF-α and activated phosphorylation of IKKα/β, IкBα, p65, JNK and p38 and the nucleus translocation of NF-кB p65 were also significantly downregulated by rPGRN. In addition, recombinant TNF-α (rTNF-α) significantly boosted TNF-α and iNOS expression vs the control group. Moreover, anti-TNF-α significantly inhibited LPS-induced TNF-α and iNOS expression. In THP-1 and BMDM cells, reversing effect of rPGRN on LPS-enhanced expressions of TNF-α and iNOS and secretion of TNF-α was further demonstrated. CONCLUSIONS: PGRN down-regulates LPS-induced macrophage M1 polarization in phenotype and function via NF-κB/MAPK signaling pathways. BioMed Central 2020-06-05 /pmc/articles/PMC7275413/ /pubmed/32503416 http://dx.doi.org/10.1186/s12865-020-00355-y Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research Article
Liu, Lianlian
Guo, Hongmei
Song, Aimei
Huang, Jiahui
Zhang, Yu
Jin, Shanshan
Li, Shutong
Zhang, Liguo
Yang, Chengzhe
Yang, Pishan
Progranulin inhibits LPS-induced macrophage M1 polarization via NF-кB and MAPK pathways
title Progranulin inhibits LPS-induced macrophage M1 polarization via NF-кB and MAPK pathways
title_full Progranulin inhibits LPS-induced macrophage M1 polarization via NF-кB and MAPK pathways
title_fullStr Progranulin inhibits LPS-induced macrophage M1 polarization via NF-кB and MAPK pathways
title_full_unstemmed Progranulin inhibits LPS-induced macrophage M1 polarization via NF-кB and MAPK pathways
title_short Progranulin inhibits LPS-induced macrophage M1 polarization via NF-кB and MAPK pathways
title_sort progranulin inhibits lps-induced macrophage m1 polarization via nf-кb and mapk pathways
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7275413/
https://www.ncbi.nlm.nih.gov/pubmed/32503416
http://dx.doi.org/10.1186/s12865-020-00355-y
work_keys_str_mv AT liulianlian progranulininhibitslpsinducedmacrophagem1polarizationvianfkbandmapkpathways
AT guohongmei progranulininhibitslpsinducedmacrophagem1polarizationvianfkbandmapkpathways
AT songaimei progranulininhibitslpsinducedmacrophagem1polarizationvianfkbandmapkpathways
AT huangjiahui progranulininhibitslpsinducedmacrophagem1polarizationvianfkbandmapkpathways
AT zhangyu progranulininhibitslpsinducedmacrophagem1polarizationvianfkbandmapkpathways
AT jinshanshan progranulininhibitslpsinducedmacrophagem1polarizationvianfkbandmapkpathways
AT lishutong progranulininhibitslpsinducedmacrophagem1polarizationvianfkbandmapkpathways
AT zhangliguo progranulininhibitslpsinducedmacrophagem1polarizationvianfkbandmapkpathways
AT yangchengzhe progranulininhibitslpsinducedmacrophagem1polarizationvianfkbandmapkpathways
AT yangpishan progranulininhibitslpsinducedmacrophagem1polarizationvianfkbandmapkpathways