Recent advancement on development of drug-induced macrophage polarization in control of human diseases

Wang, Lu; Lu, Qiumin; Gao, Wenwen; Yu, Shuwen

doi:10.1016/j.lfs.2021.119914

Cited by 24 publications

(18 citation statements)

References 220 publications

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“…14 In contrast, M2 macrophages, also designated as "activated macrophages," function in constructive processes, as tissue repair, re-epithelialization and revascularization, and produce anti-inflammatory cytokines, as IL-10, IL-4, and IL-13. 13 This series of cases indicates that, for most of their life, JXGs are formed by repairing (M2) macrophages, and are not just an M1 macrophagic response to a local antigen. The process appears to be influenced by epidermal-macrophage cross-talking, considering the tendency of these cells to accumulate against the dermoepidermal junction.…”

Section: Discussionmentioning

confidence: 94%

What is the Role of Different Macrophage Subsets in the Evolution of Juvenile Xanthogranulomas?

Wegher

Kazmarek²,

Silva³

et al. 2022

Applied Immunohistochemistry &Amp; Molecular Morphology

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There are several activated forms of macrophages: 2 main groups are designated M1 and M2. While M1 macrophages have proinflammatory, bactericidal, and phagocytic functions and are the dominant phenotype observed in the early stages of inflammation, M2 macrophages are involved in constructive processes such as tissue repair; they play a role in wound healing and are required for revascularization and re-epithelialization. Juvenile xanthogranuloma (JXG) is the most common non-Langerhans cell histiocytosis. Its pathogenesis is not well understood, but it is not considered a neoplastic entity. JXGs possibly appear as a reaction to a nonspecific injury such as trauma or viral infection, although a genetic predisposition has been suggested in some cases. Tissue damage leads to a histiocytic response. JXGs appear, evolve toward maturation, and then most of them spontaneously regress. Young JXGs are characterized by small macrophages scattered in the dermis, in apposition close to the epidermis. As the lesion matures, the number of foamy macrophages and Touton cells increases and other cell types such as plasma cells, lymphocytes, and polymorphs are observed. Regressing xanthogranulomas will show numerous spindle cells in Significant values are in bold.a storiform distribution, interstitial fibrosis, and few foamy and Touton cells. In this study, we studied the immunophenotypic profile of macrophages found in cutaneous JXGs according to their stage of maturation. We examined the skin biopsies from 25 patients; all were embedded in paraffin and stained with hematoxylin and eosin and for immunohistochemistry. Typically, all JXGs were positive for factor XIIIa and CD4, and were negative for CD1a. The following histiocyte markers were used: CD68, CD204, CD163, MAC387, and HAM56. Images were analyzed by Image J software; data were statistically evaluated by SAS 9.0 software. The cases showed a slight predominance of males and the preference of the JXGs for the axial skin. Lesions occupied the papillary and reticular dermis in 85% of the cases and extended to the subcutaneous fat in the remainder. Compared with mature and regressing JXGs, younger lesions had a higher density of M1 macrophages, stained with MAC387. This antibody labels the histiocytes that have recently arrived in the areas of inflammation. As the lesions matured, there was an overwhelming predominance of M2 macrophages. These cells tended to cluster against the epidermis, except in the 2 cases in phase of regression. This suggests that there is a cross-talk between the epidermis and macrophages and that receptors, cytokines, chemokines, and adhesion molecules may play a role in the development and evolution of JXGs. These results indicate that, for most of their life, JXGs are formed by repairing M2 macrophages and are not just an M1 macrophagic response to a local antigen. The process appears to be influenced by chemical-mediator epidermal-macrophage cross-talking, considering the tendency of these cells to accumulate against the dermoepidermal junction.

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Section: Discussionmentioning

confidence: 94%

What is the Role of Different Macrophage Subsets in the Evolution of Juvenile Xanthogranulomas?

Wegher

Kazmarek²,

Silva³

et al. 2022

Applied Immunohistochemistry &Amp; Molecular Morphology

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“…They, produce ROS and induce the production of inducible nitric oxide synthase (iNOS) and a large number of inflammatory factors such as TNF-α, IL-6 and IL-1β, and play important roles in physiopathologic processes such as killing pathogens, resistance to parasite and tumor cells, and anti-inflammatory responses. M2 macrophages, mainly produced by IL-4/IL-10/IL-13 stimulation, can be classified into multiple subtypes based on differences in induced environmental and functional typing, with immunomodulation, immunosuppression and tissue remodeling ( 13 ).…”

Section: Metabolism-related Signaling Pathways In Macrophage Polariza...mentioning

confidence: 99%

Metabolic Reprogramming Induces Macrophage Polarization in the Tumor Microenvironment

Wang

Liu

et al. 2022

Front. Immunol.

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Macrophages are one of the most important cells in the innate immune system, they are converted into two distinct subtypes with completely different molecular phenotypes and functional features under different stimuli of the microenvironment: M1 macrophages induced by IFN-γ/lipopolysaccharides(LPS) and M2 macrophages induced by IL-4/IL-10/IL-13. Tumor-associated macrophages (TAMs) differentiate from macrophages through various factors in the tumor microenvironment (TME). TAMs have the phenotype and function of M2 macrophages and are capable of secreting multiple cytokines to promote tumor progression. Both tumor cells and macrophages can meet the energy needs for rapid cell growth and proliferation through metabolic reprogramming, so a comprehensive understanding of pro-tumor and antitumor metabolic switches in TAM is essential to understanding immune escape mechanisms. This paper focuses on the functions of relevant signaling pathways and cytokines during macrophage polarization and metabolic reprogramming, and briefly discusses the effects of different microenvironments and macrophage pathogenicity, in addition to describing the research progress of inhibitory drugs for certain metabolic and polarized signaling pathways.

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“…NO is produced from L-arginine by the action of the enzyme nitric oxide synthase (NOS), playing an important role in inflammatory responses ( Förstermann and Sessa, 2012 ). Furthermore, physalins A, B, E, F, and G can inhibit the production of several inflammatory molecules, such as interleukin (IL)-1β, IL-6, IL-12, prostaglandin E 2 (PGE 2 ), and tumor necrosis factor (TNF), by activated macrophages ( Figure 3 ) ( Soares et al, 2003 ; Yang et al, 2017 ; Lin et al, 2020 ; Zhang et al, 2020 ; Wang et al, 2021b ). Most of these effects are attributed to the inhibition of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), a transcription factor involved in the regulation of several pro-inflammatory genes ( Figure 3 ) ( Jacobo-Herrera et al, 2006 ; Yang et al, 2017 ; Lin et al, 2020 ; Zhang et al, 2020 ).…”

Section: Immunomodulatory Activitymentioning

confidence: 99%

“…Physalin A, when tested in a carrageenan-induced model, significantly reduced paw edema ( Lin et al, 2020 ; Wang et al, 2021b ). In the work of Lin et al (2020) , a reduction of paw edema was achieved through the reduction of NO, TNF, and malondialdehyde (MDA) and increase in the activity of antioxidant enzymes (catalase, superoxide dismutase, and glutathione peroxidase) ( Table 2 ).…”

Section: Immunomodulatory Activitymentioning

confidence: 99%

Therapeutic Applications of Physalins: Powerful Natural Weapons

et al. 2022

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Physalins, or 16,24-cyclo-13,14-seco steroids, are compounds belonging to the class of withanolides that can be found in plants of Solanaceae family, mainly in species belonging to the genus Physalis spp., which are annual herbaceous plants widely distributed in tropical and subtropical regions of the world. Physalins are versatile molecules that act in several cell signaling pathways and activate different mechanisms of cell death or immunomodulation. A number of studies have shown a variety of actions of these compounds, including anticancer, anti-inflammatory, antiparasitic, antimicrobial, antinociceptive, and antiviral activities. Here we reviewed the main findings related to the anticancer, immunomodulatory, and antiparasitic activities of physalins and its mechanisms of action, highlighting the \challenges and future directions in the pharmacological application of physalins.

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Recent advancement on development of drug-induced macrophage polarization in control of human diseases

Cited by 24 publications

References 220 publications

What is the Role of Different Macrophage Subsets in the Evolution of Juvenile Xanthogranulomas?

What is the Role of Different Macrophage Subsets in the Evolution of Juvenile Xanthogranulomas?

Metabolic Reprogramming Induces Macrophage Polarization in the Tumor Microenvironment

Therapeutic Applications of Physalins: Powerful Natural Weapons

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