Lipoxin A4 Regulates M1/M2 Macrophage Polarization via FPR2-IRF Pathway

Abstract Lipoxin A4 (LXA4) has been shown to have anti-inflammatory activity, but its underlying molecular mechanisms are not clear. Herein, our team investigated the potential role of LXA4 in the macrophage polarisation and elucidated its possible molecular mechanism. The RAW264.7 macrophage cell line was subjected to pre-treatment with LXA4 with or without lipopolysaccharides (LPS) and interleukin-4 (IL-4). In cultured macrophages, LXA4 inhibits LPS-induced inflammatory polarization, thereby decreasing the release of proinflammation cell factors (IL-1β, IL-6, TNF-α) and increasing the release of antiinflammation cytokines (IL-4 and IL-10). Notably, the inhibitory effect of LXA4 on inflammation macrophage polarisation was related to the downregulation of p-NF-κB p65 and IRF5 activity, thereby downregulating LPS-induced phenotypic and functional polarization of macrophage M1 via the FPR2/IRF5 signaling pathway. Moreover, LXA4 also promotes the IL-4-induced polarization of M2 macrophages by promoting the FPR2/IRF4 signaling pathway. Therefore, Lipoxin A4 regulates M1/M2 polarization of macrophages via FPR2-IRF pathway.

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Eosinophils attenuate arthritis by inducing M2 macrophage polarization via inhibiting the IκB/P38 MAPK signaling pathway

Biochemical and Biophysical Research Communications ◽

10.1016/j.bbrc.2018.12.010 ◽

2019 ◽

Vol 508 (3) ◽

pp. 894-901 ◽

Cited By ~ 2

Author(s):

Liu Liu ◽

Yuanyuan Zhang ◽

Xu Zheng ◽

Li Jin ◽

Nan Xiang ◽

...

Keyword(s):

Signaling Pathway ◽

P38 Mapk ◽

Macrophage Polarization ◽

Mapk Signaling ◽

Mapk Signaling Pathway ◽

M2 Macrophage ◽

M2 Macrophage Polarization

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Blockade of the Notch Signaling Pathway Promotes M2 Macrophage Polarization to Suppress Cardiac Fibrosis Remodeling in Mice With Myocardial Infarction

Frontiers in Cardiovascular Medicine ◽

10.3389/fcvm.2021.639476 ◽

2022 ◽

Vol 8 ◽

Author(s):

Zhi Li ◽

Miao Nie ◽

Liming Yu ◽

Dengshun Tao ◽

Qiang Wang ◽

...

Keyword(s):

Myocardial Infarction ◽

Cardiac Function ◽

Notch Signaling ◽

Signaling Pathway ◽

Cardiac Fibrosis ◽

Macrophage Polarization ◽

Notch Signaling Pathway ◽

Inflammatory Factors ◽

M2 Macrophage ◽

M2 Polarization

Myocardial infarction (MI) is regarded as a serious ischemic heart disease on a global level. The current study set out to explore the mechanism of the Notch signaling pathway in the regulation of fibrosis remodeling after the occurrence of MI. First, experimental mice were infected with recombination signal binding protein J (RBP-J) shRNA and empty adenovirus vector, followed by the establishment of MI mouse models and detection of cardiac function. After 4 weeks of MI, mice in the sh-RBP-J group were found to exhibit significantly improved cardiac function relative to the sh-NC group. Moreover, knockdown of RBP-J brought about decreased infarct area, promoted cardiac macrophages M2 polarization, reduced cardiac fibrosis, and further decreased transcription and protein expressions of inflammatory factors and fibrosis-related factors. Furthermore, downregulation of cylindromatosis (CYLD) using si-CYLD reversed the results that knockdown of RBP-J inhibited fibrogenesis and the release of inflammatory factors. Altogether, our findings indicated that the blockade of Notch signaling promotes M2 polarization of cardiac macrophages and improves cardiac function by inhibiting the imbalance of fibrotic remodeling after MI.

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Convallatoxin Promotes M2 Macrophage Polarization to Attenuate Atherosclerosis Through PPARγ-Integrin αvβ5 Signaling Pathway

Drug Design Development and Therapy ◽

10.2147/dddt.s288728 ◽

2021 ◽

Vol Volume 15 ◽

pp. 803-812

Author(s):

Yi Zhang ◽

Xiujin Shi ◽

Jialun Han ◽

Wenxing Peng ◽

Zhenwei Fang ◽

...

Keyword(s):

Signaling Pathway ◽

Macrophage Polarization ◽

M2 Macrophage ◽

M2 Macrophage Polarization

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Quercetin suppresses the chymotrypsin-like activity of proteasome via inhibition of MEK1/ERK1/2 signaling pathway in hepatocellular carcinoma HepG2 cells

Canadian Journal of Physiology and Pharmacology ◽

10.1139/cjpp-2017-0655 ◽

2018 ◽

Vol 96 (5) ◽

pp. 521-526 ◽

Cited By ~ 8

Author(s):

Youming Ding ◽

Xiaoyan Chen ◽

Bin Wang ◽

Bin Yu ◽

Jianhui Ge ◽

...

Keyword(s):

Signaling Pathway ◽

P38 Mapk ◽

Protease Activity ◽

Molecular Mechanisms ◽

Inhibitory Effect ◽

Proteasome Activity ◽

Flavonoid Compound ◽

Jnk Signaling ◽

Promising Target ◽

Jnk Signaling Pathway

The proteasomal system is a promising target for cancer treatment. Quercetin (Que), a flavonoid compound with antitumor ability, displays the inhibitory effect on proteasome activity. However, the underlying molecular mechanisms are ill defined. The present study found that Que treatment significantly reduced the chymotrypsin-like protease activity of proteasome whereas the trypsin- and caspase-like protease activities remained unchanged in HepG2 cancer cells, along with activation of p38 MAPK and JNK and reduction of ERK1/2 phosphorylation. Que-reduced proteasome activity could not be reverted by inhibition of p38 MAPK and JNK signaling pathway. In addition, MEK1 overexpression or knockdown upregulated or downregulated the chymotrypsin-like protease activity of proteasome, respectively. Both Que and MEK1/ERK1/2 inhibitor attenuated the expression levels of proteasome β subunits. These results indicate that Que-induced suppression of MEK1/ERK1/2 signaling and subsequent reduction of proteasome β subunits is responsible for its inhibitory impacts on proteasome activity.

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Interleukin 26 Skews Macrophage Polarization Towards M1 Phenotype by Activating cJUN and the NF-κB Pathway

Cells ◽

10.3390/cells9040938 ◽

2020 ◽

Vol 9 (4) ◽

pp. 938

Author(s):

Yi-Hsuan Lin ◽

Yi-Hsun Wang ◽

Yi-Jen Peng ◽

Feng-Cheng Liu ◽

Gu-Jiun Lin ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Messenger Rna ◽

Molecular Mechanisms ◽

Macrophage Polarization ◽

Enzyme Linked Immunosorbent Assay ◽

M2 Macrophage ◽

Macrophage Differentiation ◽

Macrophage Cells ◽

M1 Macrophage ◽

Interleukin 26

Interleukin 26 (IL-26) is a new member of the IL-10 family that is highly expressed in rheumatoid arthritis (RA). However, the functions of IL-26 produced by macrophages in RA have not been elucidated. In the present work, we evaluated the effects and the mechanisms of IL-26 on M1 and M2 macrophage differentiation. Human or mouse macrophage cells were treated with lipopolysaccharides (LPS), interferon gamma (IFNγ), or IL-4 alone or concurrently treated with IL-26 to monitor M1 or M2 macrophage subtypes. The expression level of M1 or M2 macrophage genes was evaluated by reverse transcription polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). The molecular mechanisms of downstream signaling activation during differentiation were investigated by immunoblotting assay. Our results found that IL-26 promoted macrophage cells from CD80+ M1 macrophage differentiation, not from the CD206+ M2 phenotype. The messenger RNA of M1-type macrophage markers tumor necrosis factor alpha (TNFα) and inducible nitric oxide synthase (iNOS) was up-regulated in the IL-26-treated group. Also, the M1-related proinflammatory cytokines TNFα and IL-6 were induced after IL-26 stimulation. Interestingly, IL-10, a cytokine marker of M2 macrophage, was also elevated after IL-26 stimulation. Moreover, the M1-like macrophage stimulated by IL-26 underwent cJUN, nuclear factor kappa B (NF-κB), and signal transducer and activator of transcription 1 (STAT1) activation. Our findings suggested the role of IL-26 in synovial macrophages of active rheumatoid arthritis and provided a new insight into IL-26 as a candidate therapeutic target in rheumatoid arthritis.

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Eugenol Inhibits Sodium Currents in Dental Afferent Neurons

Journal of Dental Research ◽

10.1177/154405910608501005 ◽

2006 ◽

Vol 85 (10) ◽

pp. 900-904 ◽

Cited By ~ 56

Author(s):

C.-K. Park ◽

H.Y. Li ◽

K.-Y. Yeon ◽

S.J. Jung ◽

S.-Y. Choi ◽

...

Keyword(s):

Molecular Mechanisms ◽

Transient Receptor Potential ◽

Receptor Potential ◽

Inhibitory Effect ◽

Transient Receptor Potential Vanilloid ◽

Afferent Neurons ◽

Patch Clamp Technique ◽

Independent Manner ◽

Pre Treatment ◽

Transient Receptor

Although eugenol is widely used in dentistry, little is known about the molecular mechanisms responsible for its anesthetic properties. In addition to calcium channels, recently demonstrated by our group, there could be another molecular target for eugenol. Using a whole-cell patch-clamp technique, we investigated the effect of eugenol on voltage-gated sodium channel currents ( I Na) in rat dental primary afferent neurons identified by retrograde labeling with a fluorescent dye in maxillary molars. Eugenol inhibited action potentials and I Na in both capsaicin-sensitive and capsaicin-insensitive neurons. The pre-treatment with capsazepine, a competitive antagonist of transient receptor potential vanilloid 1 (TRPV1), failed to block the inhibitory effect of eugenol on I Na, suggesting no involvement of TRPV1. Two types of I Na, tetrodotoxin (TTX)-resistant and TTX-sensitive I Na, were inhibited by eugenol. Our results demonstrated that eugenol inhibits I Na in a TRPV1-independent manner. We suggest that I Na inhibition by eugenol contributes to its analgesic effect.

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Tumor-derived exosomal miR-934 induces macrophage M2 polarization to promote liver metastasis of colorectal cancer

Journal of Hematology & Oncology ◽

10.1186/s13045-020-00991-2 ◽

2020 ◽

Vol 13 (1) ◽

Author(s):

Senlin Zhao ◽

Yushuai Mi ◽

Bingjie Guan ◽

Binbin Zheng ◽

Ping Wei ◽

...

Keyword(s):

Colorectal Cancer ◽

Liver Metastasis ◽

Molecular Mechanisms ◽

Macrophage Polarization ◽

In Vitro Assays ◽

Luciferase Reporter ◽

M2 Macrophage ◽

M2 Macrophages ◽

Premetastatic Niche ◽

Niche Formation

Abstract Background Mounting evidence has demonstrated the vital importance of tumor-associated macrophages (TAMs) and exosomes in the formation of the premetastatic niche. However, the molecular mechanisms by which tumor-derived exosomal miRNAs interact with TAMs underlying premetastatic niche formation and colorectal cancer liver metastasis (CRLM) remain largely unknown. Methods Transmission electron microscopy and differential ultracentrifugation were used to verify the existence of exosomes. In vivo and in vitro assays were used to identify roles of exosomal miR-934. RNA pull-down assay, dual-luciferase reporter assay, etc. were applied to clarify the mechanism of exosomal miR-934 regulated the crosstalk between CRC cells and M2 macrophages. Results In the present study, we first demonstrated the aberrant overexpression of miR-934 in colorectal cancer (CRC), especially in CRLM, and its correlation with the poor prognosis of CRC patients. Then, we verified that CRC cell-derived exosomal miR-934 induced M2 macrophage polarization by downregulating PTEN expression and activating the PI3K/AKT signaling pathway. Moreover, we revealed that hnRNPA2B1 mediated miR-934 packaging into exosomes of CRC cells and then transferred exosomal miR-934 into macrophages. Interestingly, polarized M2 macrophages could induce premetastatic niche formation and promote CRLM by secreting CXCL13, which activated a CXCL13/CXCR5/NFκB/p65/miR-934 positive feedback loop in CRC cells. Conclusions These findings indicate that tumor-derived exosomal miR-934 can promote CRLM by regulating the crosstalk between CRC cells and TAMs. These findings reveal a tumor and TAM interaction in the metastatic microenvironment mediated by tumor-derived exosomes that affects CRLM. The present study also provides a theoretical basis for secondary liver cancer.

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Interleukin-4-Clicked Surfaces Drive M2 Macrophage Polarization

ChemBioChem ◽

10.1002/cbic.201600480 ◽

2016 ◽

Vol 17 (22) ◽

pp. 2123-2128 ◽

Cited By ~ 9

Author(s):

Tessa Lühmann ◽

Valerie Spieler ◽

Vera Werner ◽

Marie-Gabrielle Ludwig ◽

Juliane Fiebig ◽

...

Keyword(s):

Macrophage Polarization ◽

Interleukin 4 ◽

M2 Macrophage ◽

M2 Macrophage Polarization

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Exosomes secreted by FNDC5-BMMSCs protect myocardial infarction by anti-inflammation and macrophage polarization via NF-κB signaling pathway and Nrf2/HO-1 Axis

10.21203/rs.3.rs-754264/v1 ◽

2021 ◽

Author(s):

Hogjuan Ning ◽

Haixu Chen ◽

Jingyu Deng ◽

Chun Xiao ◽

Lina Shan ◽

...

Keyword(s):

Myocardial Infarction ◽

Signaling Pathway ◽

Transmembrane Protein ◽

Macrophage Polarization ◽

M2 Macrophage ◽

Therapeutic Effects ◽

Cell Based Therapy ◽

Anti Inflammation

Abstract Background Exosomes are considered a substitute for stem cell-based therapy for myocardial infarction (MI). FNDC5, a transmembrane protein located in the cytoplasm, plays a crucial role in inflammation diseases and MI repair. Furthermore, our previous study found that FNDC5 pre-conditioning bone marrow-derived mesenchymal stem cells (BMMSCs) could secreted more exosomes, but little was known on MI repair. Methods Exosomes isolated from BMMSCs with or without FNDC5-OV were injected into infarcted hearts. Then, cardiomyocytes apoptosis, and inflammation responses were detected. Furthermore, exosomes were administrated to RAW264.7 macrophage with LPS treatment to investigate its effect on inflammation and macrophage polarization. Results Compared with MSCs-Exo, FNDC5-MSCs-Exo had superior therapeutic effects on anti-inflammation and anti-apoptosis, as well as polarizing M2 macrophage in vivo. Meanwhile, the in vitro results also showed that FNDC5-MSCs–Exo decreased pro-inflammatory secretion and increased anti-inflammatory secretion under LPS stimulation, which partly depressed NF-κB signaling pathway and upregulated Nrf2/HO-1 Axis. Conclusions FNDC5-BMMSCs-derived exosomes play anti-inflammation effects and promote M2 macrophage polarization via NF-κB signaling pathway and Nrf2/HO-1 Axis, which may develop a promising cell-free therapy for MI.

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