Modulation of Wnt/β-catenin signaling in IL-17A-mediated macrophage polarization of RAW264.7 cells

Macrophages play pivotal roles in host defense and immune homeostasis, which have two major functional polarization states, the classically activated M1 and the alternatively activated M2. Interleukin (IL)-17A is an immune modulator able to shape macrophage phenotypes. Wnt/β-catenin is a development...

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Main Authors: Chao Yuan, Dandan Yang, Jia Ma, Jiali Yang, Jing Xue, Fuyang Song, Xiaoming Liu
Format: Article
Language:English
Published: Associação Brasileira de Divulgação Científica 2020-06-01
Series:Brazilian Journal of Medical and Biological Research
Subjects:
Online Access:http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2020000800604&tlng=en
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author Chao Yuan
Dandan Yang
Jia Ma
Jiali Yang
Jing Xue
Fuyang Song
Xiaoming Liu
author_facet Chao Yuan
Dandan Yang
Jia Ma
Jiali Yang
Jing Xue
Fuyang Song
Xiaoming Liu
author_sort Chao Yuan
collection DOAJ
description Macrophages play pivotal roles in host defense and immune homeostasis, which have two major functional polarization states, the classically activated M1 and the alternatively activated M2. Interleukin (IL)-17A is an immune modulator able to shape macrophage phenotypes. Wnt/β-catenin is a developmental signaling pathway that plays crucial roles in morphogenesis and tissue homeostasis, which has also been recently demonstrated playing roles in immune regulation. A growing amount of evidence suggests that both Wnt and IL-17A signaling are involved in macrophage polarization. However, their interaction in macrophage polarization remains elusive. The aim of present study was to explore impacts of Wnt/β-catenin on IL-17A-mediated macrophage M1/M2 polarization in murine monocyte/macrophage-like cell line RAW264.7. Results revealed that IL-17A activated Wnt/β-catenin signaling and induced macrophage M1 polarization, but inhibited M2 polarization. In contrast, the activation of Wnt/β-catenin signaling led to the inhibition of M1 macrophage polarization but the promotion of M2 polarization. Importantly, the activation of Wnt/β-catenin also showed abilities to inhibit the IL-17A-induced M1 macrophage polarization while diminishing the IL-17A-inhibited M2 polarization. Molecular analysis further uncovered that the JAK/STAT signaling pathway was involved in the interaction of Wnt/β-catenin and IL-17A in the modulation of macrophage polarization. These results suggested that the Wnt/β-catenin signaling modulated IL-17A-altered macrophage polarization in part by regulating the JAK/STAT signaling pathway. This study thus revealed a novel function of Wnt/β-catenin signaling in regulating IL-17A-altered macrophage polarization.
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spelling doaj.art-4b27af6666a1426abd11d8706a8951232022-12-21T19:36:16ZengAssociação Brasileira de Divulgação CientíficaBrazilian Journal of Medical and Biological Research1414-431X2020-06-0153810.1590/1414-431x20209488Modulation of Wnt/β-catenin signaling in IL-17A-mediated macrophage polarization of RAW264.7 cellsChao Yuanhttps://orcid.org/0000-0003-2311-1435Dandan Yanghttps://orcid.org/0000-0001-9683-4314Jia Mahttps://orcid.org/0000-0002-5621-8645Jiali Yanghttps://orcid.org/0000-0002-7316-9259Jing Xuehttps://orcid.org/0000-0002-7143-0011Fuyang Songhttps://orcid.org/0000-0002-0276-5926Xiaoming Liuhttps://orcid.org/0000-0002-3902-9105Macrophages play pivotal roles in host defense and immune homeostasis, which have two major functional polarization states, the classically activated M1 and the alternatively activated M2. Interleukin (IL)-17A is an immune modulator able to shape macrophage phenotypes. Wnt/β-catenin is a developmental signaling pathway that plays crucial roles in morphogenesis and tissue homeostasis, which has also been recently demonstrated playing roles in immune regulation. A growing amount of evidence suggests that both Wnt and IL-17A signaling are involved in macrophage polarization. However, their interaction in macrophage polarization remains elusive. The aim of present study was to explore impacts of Wnt/β-catenin on IL-17A-mediated macrophage M1/M2 polarization in murine monocyte/macrophage-like cell line RAW264.7. Results revealed that IL-17A activated Wnt/β-catenin signaling and induced macrophage M1 polarization, but inhibited M2 polarization. In contrast, the activation of Wnt/β-catenin signaling led to the inhibition of M1 macrophage polarization but the promotion of M2 polarization. Importantly, the activation of Wnt/β-catenin also showed abilities to inhibit the IL-17A-induced M1 macrophage polarization while diminishing the IL-17A-inhibited M2 polarization. Molecular analysis further uncovered that the JAK/STAT signaling pathway was involved in the interaction of Wnt/β-catenin and IL-17A in the modulation of macrophage polarization. These results suggested that the Wnt/β-catenin signaling modulated IL-17A-altered macrophage polarization in part by regulating the JAK/STAT signaling pathway. This study thus revealed a novel function of Wnt/β-catenin signaling in regulating IL-17A-altered macrophage polarization.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2020000800604&tlng=enWnt/β-catenin signalingInterleukin-17AMacrophage polarizationSTATImmune regulation
spellingShingle Chao Yuan
Dandan Yang
Jia Ma
Jiali Yang
Jing Xue
Fuyang Song
Xiaoming Liu
Modulation of Wnt/β-catenin signaling in IL-17A-mediated macrophage polarization of RAW264.7 cells
Brazilian Journal of Medical and Biological Research
Wnt/β-catenin signaling
Interleukin-17A
Macrophage polarization
STAT
Immune regulation
title Modulation of Wnt/β-catenin signaling in IL-17A-mediated macrophage polarization of RAW264.7 cells
title_full Modulation of Wnt/β-catenin signaling in IL-17A-mediated macrophage polarization of RAW264.7 cells
title_fullStr Modulation of Wnt/β-catenin signaling in IL-17A-mediated macrophage polarization of RAW264.7 cells
title_full_unstemmed Modulation of Wnt/β-catenin signaling in IL-17A-mediated macrophage polarization of RAW264.7 cells
title_short Modulation of Wnt/β-catenin signaling in IL-17A-mediated macrophage polarization of RAW264.7 cells
title_sort modulation of wnt β catenin signaling in il 17a mediated macrophage polarization of raw264 7 cells
topic Wnt/β-catenin signaling
Interleukin-17A
Macrophage polarization
STAT
Immune regulation
url http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2020000800604&tlng=en
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