Advances in the role of STAT3 in macrophage polarization

Xia, Tingting; Zhang, Meng; Lei, Wei; Yang, Renqiang; Fu, Sheng-Ping; Fan, Zhenhai; Yang, Ying; Zhang, Tao

doi:10.3389/fimmu.2023.1160719

Cited by 74 publications

(23 citation statements)

References 124 publications

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“…While it is necessary to consider that macrophages are an extremely plastic cell population and the membrane-bound markers and cytokines assessed here are not sufficient to affirm a bona-fide complete engagement of macrophages into a permanent well-defined sub-type, our results suggest that IL-6 (4 CH) could contribute to the promotion of an M2a-like phenotype. These results could be in accordance with the fact that IL-6 is known to trigger STAT3 signaling [ 51 ], and that the latter has been reported to be involved in M2a polarization [ 52 ]. Interestingly enough, Fernando et al have already documented that, when combined with IL-4 and IL-13, IL-6 enhanced the polarization of alternatively activated macrophages, based on their increased expression of arginase-1, Ym1, and CD206 [ 53 ].…”

Section: Discussionsupporting

confidence: 87%

In Vitro Study of Interleukin-6 when Used at Low Dose and Ultra-Low Dose in Micro-Immunotherapy

Jacques,

Marchand,

Chatelais

et al. 2024

Life

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As one of the major cytokines implicated in the orchestration of immune responses, interleukin 6 (IL-6) can either act as a pro- or an anti-inflammatory factor, depending on the micro-environment. In micro-immunotherapy (MI) medicines, IL-6 is employed at low doses (LD) and ultra-low doses (ULD), expressed in centesimal Hahnemannian (CH), and used alone or in combination with other immune regulators to modulate patients’ immune responses. The present study focused on assessing the in vitro immune-modulatory effects of two IL-6-containing MI products: (i) the unitary IL-6 (4 CH) and (ii) the complex MI-medicine (MIM) 2LALERG®, which includes IL-6 (17 CH) in association with other actives in its formulation. Our results showed that IL-6 (4 CH) activated granulocytes under basal conditions, and natural killer cells in the presence of an anti-CD3 signal, as assessed by their CD69 expression. In addition, IL-6 (4 CH) balanced the macrophages’ differentiation toward a M2a profile. On the other hand, the tested 2LALERG® capsule inhibited the histamine degranulation of rats’ peritoneal mast cells and reduced the release of IL-6 itself in inflamed human macrophages. Altogether, these data provide novel pieces of evidence on the double-edged potential of the LD and ULD of IL-6 in immune responses modulation, when employed in MI.

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Section: Discussionsupporting

confidence: 87%

In Vitro Study of Interleukin-6 when Used at Low Dose and Ultra-Low Dose in Micro-Immunotherapy

Jacques,

Marchand,

Chatelais

et al. 2024

Life

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“…Alveolar macrophages are considered a therapeutic target because they are poised to rapidly release large amounts of inflammatory cytokines in response to LPS [24]. Several studies have shown that suppressing alveolar macrophage STAT3 phosphorylation, thereby reducing the production of pro-inflammatory cytokine, such as IL-6, TNF-α, IL-1β, a cytokine known to be involved in the pathogenesis of inflammatory lung disease [25]. In our study, we showed that lung injury score was significantly reduced by Niclosamide administration in LPS-induced mice.…”

Section: Discussionmentioning

confidence: 99%

Protective Effect of Niclosamide on Lipopolysaccharide-induced Sepsis in Mice by Modulating STAT3 Pathway

JANG

2023

Korean J Clin Lab Sci

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Sepsis is a systemic inflammatory response, with manifestations in multiple organs by pathogenic infection. Currently, there are no promising therapeutic strategies. Signal transducer and activator of transcription 3 (STAT3) is a cell signaling transcription factor. Niclosamide is an anti-helminthic drug approved by the Food and Drug Administration (FDA) as a potential STAT3 inhibitor. C57BL/6 mice were treated with an intraperitoneal injection of lipopolysaccharide (LPS). Niclosamide was administered orally 2 hours after the LPS injection. This study found that Niclosamide improved the survival and lung injury of LPS-induced mice. Niclosamide decreased the levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) in serum. The effects of Niclosamide on phosphoinositide 3-kinase (PI3K), AKT, nuclear factor-κB (NF-κB), and STAT3 signaling pathways were determined in the lung tissue by immunoblot analysis. Niclosamide reduced phosphorylation of PI3K, AKT, NF-κB, and STAT3 significantly. Furthermore, it reduced the phosphorylation of STAT3 by LPS stimulation in RAW 264.7 macrophages. Niclosamide also reduced the LPS-stimulated expression of proinflammatory mediators, including IL-6, TNF-α, and IL-1β. Niclosamide provides a new therapeutic strategy for murine sepsis models by suppressing the inflammatory response through STAT3 inhibition.

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“…STATs are crucial transcription factors in macrophage polarization, with STAT1 being integral to M1, and STAT3/6 to M2 polarization. [ 145 ]. In cervical cancer, FGD5-AS1, via the miR-129-5p/bone marrow stromal cell antigen 2 (BST2) axis, promotes tumor growth and M2 polarization [ 146 ].…”

Section: Lncrnas That Modulate Macrophage Nf-κb Activity In Cancermentioning

confidence: 99%

Roles of lncRNAs in NF-κB-Mediated Macrophage Inflammation and Their Implications in the Pathogenesis of Human Diseases

Shin,

Park,

Shin

et al. 2024

IJMS

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Over the past century, molecular biology’s focus has transitioned from proteins to DNA, and now to RNA. Once considered merely a genetic information carrier, RNA is now recognized as both a vital element in early cellular life and a regulator in complex organisms. Long noncoding RNAs (lncRNAs), which are over 200 bases long but do not code for proteins, play roles in gene expression regulation and signal transduction by inducing epigenetic changes or interacting with various proteins and RNAs. These interactions exhibit a range of functions in various cell types, including macrophages. Notably, some macrophage lncRNAs influence the activation of NF-κB, a crucial transcription factor governing immune and inflammatory responses. Macrophage NF-κB is instrumental in the progression of various pathological conditions including sepsis, atherosclerosis, cancer, autoimmune disorders, and hypersensitivity. It orchestrates gene expression related to immune responses, inflammation, cell survival, and proliferation. Consequently, its malfunction is a key contributor to the onset and development of these diseases. This review aims to summarize the function of lncRNAs in regulating NF-κB activity in macrophage activation and inflammation, with a particular emphasis on their relevance to human diseases and their potential as therapeutic targets. The insights gained from studies on macrophage lncRNAs, as discussed in this review, could provide valuable knowledge for the development of treatments for various pathological conditions involving macrophages.

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Advances in the role of STAT3 in macrophage polarization

Cited by 74 publications

References 124 publications

In Vitro Study of Interleukin-6 when Used at Low Dose and Ultra-Low Dose in Micro-Immunotherapy

In Vitro Study of Interleukin-6 when Used at Low Dose and Ultra-Low Dose in Micro-Immunotherapy

Protective Effect of Niclosamide on Lipopolysaccharide-induced Sepsis in Mice by Modulating STAT3 Pathway

Roles of lncRNAs in NF-κB-Mediated Macrophage Inflammation and Their Implications in the Pathogenesis of Human Diseases

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