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

Yuan, Chao; Yang, Dandan; Ma, Jia; Yang, Jiali; Xue, Jing; Song, Fuyang; Liu, Xiaoming

doi:10.1590/1414-431x20209488

Cited by 19 publications

(19 citation statements)

References 34 publications

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“…The Wnt pathway is reported to regulate the pro-or antiinflammatory phenotype alteration of macrophages. Wnt3a (Feng et al, 2018b;Yuan et al, 2020) or Wnt5a (Feng et al, 2018a) treatment could alter cytokine-stimulated macrophage polarization, thereby predisposing macrophages to the M2 phenotype. LPSinduced proinflammatory cytokine expression in macrophages was abolished after β-catenin knockdown (Fang et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Inhibition of BCL9 Modulates the Cellular Landscape of Tumor-Associated Macrophages in the Tumor Immune Microenvironment of Colorectal Cancer

et al. 2021

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Tumor-associated macrophages (TAMs) are an indispensable part of the tumor microenvironment (TME), and they likely play a negative rather than positive role in cancer treatment. However, the cellular landscape and transcriptional profile regulation of TAMs in the case of tumor gene inactivation or chemical interference remains unclear. The B-cell lymphoma 9/B-cell lymphoma 9-like (BCL9/BCL9L) is a critical transcription co-factor of β-catenin. Suppression of Bcl9 inhibits tumor growth in mouse models of colorectal cancer (CRC). Here, we studied the TAMs of CRC by single-cell sequencing. Bcl9 depletion caused macrophage polarization inhibition from M0 to M2 and changed the CRC TME, which further interferes with the inflammation of M0 and M1. The transcription factor regulating these processes may be related to the Wnt signaling pathway from multiple levels. Furthermore, we also found that the cells delineated from monocyte to NK-like non-functioning cells were significantly different in the BCL9-deprived population. Combining these data, we proposed a TAM-to-NK score to evaluate the dynamic balance in TME of monocyte/TAM cells and NK-like non-functioning cells in The Cancer Genome Atlas (TCGA) clinical samples to verify the clinical significance. We demonstrated that the cell type balance and transcription differences of TAMs regulated by BCL9-driven Wnt signaling affected immune surveillance and inflammation of cancer, ultimately affecting patients’ prognosis. We thereby highlighted the potential of targeting Wnt signaling pathway through cancer immunotherapy.

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Section: Introductionmentioning

confidence: 99%

Inhibition of BCL9 Modulates the Cellular Landscape of Tumor-Associated Macrophages in the Tumor Immune Microenvironment of Colorectal Cancer

et al. 2021

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“…As known to all, macrophages are crucial adjuster of innate and adaptive immune responses, and have been identified as important angiogenic effector cells that capable of modulating neovascularization [ 33 ]. Numerous previous research showed that IL-17A, as a pro-inflammatory cytokine, is involved in macrophage polarization which could induce M1 macrophage polarization but mitigate M2 polarization, by which IL-17A increased RNV in ischemic retinopathy [ 7 , 34 ]. In this study, results showed that IL-17A was notably increased in retinas of OIR mice at P17, as well as in primary BMDMs cultured under hypoxic conditions for 12 h. Besides, immunofluorescent staining showed that IL-17A expressed in retinal macrophages of OIR models.…”

Section: Discussionmentioning

confidence: 99%

Blocking the interaction between interleukin-17A and endoplasmic reticulum stress in macrophage attenuates retinal neovascularization in oxygen-induced retinopathy

Wang

Gao

et al. 2021

Cell Biosci

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Background Neovascularization is a leading cause of visual loss typically associated with diabetic retinopathy (DR) and retinopathy of prematurity (ROP). Interleukin-17A (IL-17A) and endoplasmic reticulum (ER) stress both have been demonstrated to play a proangiogenic role in ischemic retinopathies. However, the relationship between IL-17A and ER stress in retinal neovascularization (RNV) under hypoxic conditions and its underlying mechanisms remain unclear. Methods In this study, oxygen-induced retinopathy (OIR) mice model was established and intravitreal injections were conducted. Changes of IL-17A and ER stress markers in retinas and cultured primary bone marrow derived macrophage (BMDM) under normoxic or hypoxic conditions were detected. Western blotting, Real-Time RT-PCR, Immunofluorescence assays were conducted to explore the roles and relationship of IL-17A and ER stress in RNV, as well as its underlying mechanisms. Results Compared to that in normal controls, IL-17A and ER stress markers were all remarkably increased under hypoxic conditions both in vivo and in vitro. Neutralization or knock out of IL-17A decreased ER stress. ER stress inhibitor 4-phenylbutyrate (4-PBA), attenuated the production of IL-17A, suggesting a positive feedback loop between IL-17A and ER stress. Inhibition of IL-17A or ER stress decreased areas of nonperfusion and neovascularization in OIR retinas. As TXNIP/NLRP3 pathway activation has been demonstrated to be involved in increased retinal vascular permeability of ischemic retinopathy, we observed that TXNIP/NLRP3 pathway mediated in the interaction between IL-17A and ER stress under hypoxic conditions. Conclusion The interplay between IL-17A and ER stress contributes to RNV in macrophages via modulation of TXNIP/NLRP3 signaling pathway under hypoxic conditions. The feedback loops may become an innovative and multiple pharmacological therapeutic target for ischemic retinopathy.

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“…Our results showed that CDC42 expression was positively associated with the Wnt signaling pathway. The Wnt signaling pathway, a key cell proliferation and differentiation pathway, has been associated with dysregulated macrophage activity in disease [40][41][42]. For instance, the activation of Wnt/β-catenin signaling leads to the inhibition of M1 macrophage polarization but the promotion of M2 polarization [42].…”

Section: Cdc42 Positively Associated With Wnt Signaling Pathwaymentioning

confidence: 99%

Identification of hepatocellular carcinoma-related genes associated with macrophage differentiation based on bioinformatics analyses

et al. 2021

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Macrophage differentiation is associated with tumorigenesis, including the tumorigenesis of hepatocellular carcinoma (HCC). Herein, we explored the value of macrophage differentiation-associated genes (MDGs) in the prognosis of HCC using data from The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC) databases. We performed multivariate Cox regression analyses to identify the hub genes affecting HCC patient prognoses. The correlations between hub genes and macrophage differentiation and immune checkpoint inhibitors (PD-1, PD-L1, and CTLA4) were investigated. Finally, the potential mechanism was examined with gene set enrichment analysis (GSEA). In total, seventeen differentially expressed MDGs were obtained after intersecting data from the two databases. Multivariate analysis indicated that CDC42 expression was an independent prognostic indicator in both databases. Furthermore, CDC42 showed a strong correlation with the tumor infiltration levels of immune cells in HCC tissue. Correlation analysis revealed that CDC42 expression was positively associated with M2 macrophage markers and immune checkpoint inhibitors, which indicated that CDC42 expression might be related to M2 macrophage differentiation and HCC cell immune tolerance. Finally, GSEA showed that CDC42 expression was most significantly related to the Wnt signaling pathway. In conclusion, this study showed that CDC42 expression might be an important MDG in HCC and may prove to be a new gene for studying macrophage differentiation in HCC. Abbreviations : HCC: hepatocellular carcinoma; TCGA: The Cancer Genome Atlas; ICGC: International Cancer Genome Consortium; GSEA: gene set enrichment analysis; GO: Gene Ontology; KEGG: Kyoto Encyclopedia of Genes and Genomes; ROC: receiver operating characteristic; K-M: Kaplan-Meier; AUC: the area under the ROC curve; TNM: Tumor size/lymph nodes/distance metastasis

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

Cited by 19 publications

References 34 publications

Inhibition of BCL9 Modulates the Cellular Landscape of Tumor-Associated Macrophages in the Tumor Immune Microenvironment of Colorectal Cancer

Inhibition of BCL9 Modulates the Cellular Landscape of Tumor-Associated Macrophages in the Tumor Immune Microenvironment of Colorectal Cancer

Blocking the interaction between interleukin-17A and endoplasmic reticulum stress in macrophage attenuates retinal neovascularization in oxygen-induced retinopathy

Identification of hepatocellular carcinoma-related genes associated with macrophage differentiation based on bioinformatics analyses

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