The pentacyclic triterpene Lupeol switches M1 macrophages to M2 and ameliorates experimental inflammatory bowel disease

Zhu, Ye; Li, Xueqing; Chen, Jianquan; Chen, Tongjun; Shi, Zhimin; Lei, Miaona; Zhang, Yanjun; Bai, Peng; Li, Yi-Fang; Xuan, Fu‐Zhen

doi:10.1016/j.intimp.2015.11.031

Cited by 119 publications

(78 citation statements)

References 49 publications

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“…IRF-5 protein, which promotes M1 polarization, was significantly reduced via inhibition of p38 MAPK phosphorylation. It was suggested that soluble factors that are released by M1 macrophages were responsible for disruption of epithelial integrity by reducing ZO-1 (Zonula occludens-1) expression, with the effect being reversed by Lupeol [41]. …”

Section: Role Of Macrophages In Intestinal and Colorectal Diseasementioning

confidence: 99%

Chemopreventive Effects of Phytochemicals and Medicines on M1/M2 Polarized Macrophage Role in Inflammation-Related Diseases

Koh

Yang

Lai

et al. 2018

IJMS

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Macrophages can polarize into two different states (M1 and M2), which play contrasting roles during pathogenesis or tissue damage. M1 polarized macrophages produce pro-inflammatory cytokines and mediators resulting in inflammation, while M2 macrophages have an anti-inflammatory effect. Secretion of appropriate cytokines and chemokines from macrophages can lead to the modification of the microenvironment for bridging innate and adaptive immune responses. Increasing evidence suggests that polarized macrophages are pivotal for disease progression, and the regulation of macrophage polarization may provide a new approach in therapeutic treatment of inflammation-related diseases, including cancer, obesity and metabolic diseases, fibrosis in organs, brain damage and neuron injuries, and colorectal disease. Polarized macrophages affect the microenvironment by secreting cytokines and chemokines while cytokines or mediators that are produced by resident cells or tissues may also influence macrophages behavior. The interplay of macrophages and other cells can affect disease progression, and therefore, understanding the activation of macrophages and the interaction between polarized macrophages and disease progression is imperative prior to taking therapeutic or preventive actions. Manipulation of macrophages can be an entry point for disease improvement, but the mechanism and potential must be understood. In this review, some advanced studies regarding the role of macrophages in different diseases, potential mechanisms involved, and intervention of drugs or phytochemicals, which are effective on macrophage polarization, will be discussed.

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Section: Role Of Macrophages In Intestinal and Colorectal Diseasementioning

confidence: 99%

Chemopreventive Effects of Phytochemicals and Medicines on M1/M2 Polarized Macrophage Role in Inflammation-Related Diseases

Koh

Yang

Lai

et al. 2018

IJMS

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“…Zhu et al [32] suggest that disequilibrium of macrophage subpopulations promotes colitis development. Besides, either switching M1 to M2 macrophages or transfer of M2 macrophages ameliorates experimental colitis [32][33][34].…”

Section: Discussionmentioning

confidence: 99%

Crohn’s Disease Patients with Depression Exhibit Alterations in Monocyte/Macrophage Phenotype and Increased Proinflammatory Cytokine Production

Tang

Zhao

Lei

et al. 2019

Dig Dis

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Background: Crohn's disease (CD) is strongly associated with depression, but the mechanisms underlying this relationship are not fully understood. Recently, neuroimmunological studies have demonstrated that proinflammatory monocytes/macrophages play a key role in the pathogenesis of depression. The present study investigates monocyte/macrophage phenotypes and plasma cytokine levels in CD. Methods: Eligible CD patients were divided into nondepressed and depressed groups according to Hospital Anxiety and Depression Scale for depression (HADS-D). The Harvey-Bradshaw index (HBI), the Simple Endoscopic Score for Crohn's disease (SES-CD), and the Global Histological Disease Activity Score (GHAS) were compared between the 2 groups. Immunohistochemistry was performed to quantify the expression of CD68, inducible nitic oxide synthase (iNOS), and CD163 in colon mucosa. Enzyme-linked Immunosorbent Assay was used to detect plasma levels of M1 macrophage-secreted cytokines (tumor necrosis factor [TNF]-α, interleukin 6 [IL-6], IL-1β) and M2 cytokines (transforming growth factor [TGF]-β1, IL-10, C-C motif chemokine ligand 22, [CCL22]). Flow cytometry was utilized to determine peripheral blood monocyte subsets. Results: Depressed CD patients (n = 91) presented higher HBI, SES-CD, GHAS than the nondepressed patients (n = 42). Intermediate (CD14++CD16+) and nonclassical monocytes (CD14+CD16++) percentages, integrated optical density (IOD) of iNOS+ cells representing M1 macrophages, and plasma levels of TNF-α, IL-6, IL-1β were increased while classical monocyte (CD14++CD16-) percentage, IOD of CD163+ cells representing M2 macrophages, and IL-10 plasma levels were decreased in depressed versus nondepressed CD patients. Plasma levels of TNF-α, IL-6, IL-1β correlated with HADS-D scores. Conclusion: Monocytes subpopulation disequilibrium toward intermediate and nonclassic phenotypes and macrophage polarization toward M1 phenotype with increased proinflammatory cytokine release are more likely to be found in CD patients with depressive symptoms.

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“…Re-polarization of macrophages is a key role and a promising therapeutic option in many diseases (26, 82). For example, inflammatory bowel diseases can be ameliorated by switching M1 macrophages to M2 (83, 84). Conversion of M2 to M1 phenotype is a potential therapeutic intervention in anti-tumor (85, 86).…”

Section: Discussionmentioning

confidence: 99%

Immunomodulatory activity of Ganoderma lucidum immunomodulatory protein via PI3K/Akt and MAPK signaling pathways in macrophage RAW264.7 cells

Chang

et al. 2018

Preprint

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Ganoderma lucidum, a traditional edible and medicinal fungus, holds an important status in health care systems in China and other Asian countries. Fungal immunomodulatory protein (FIP), one of the active ingredients isolated from G. lucidum, is a class of naturally occurring proteins and possesses potential biological functions. This study was conducted to explore the molecular mechanism of its immunomodulatory potency in immune responses of macrophages. In vitro assays of biological activity indicated that rFIP-glu significantly activated macrophage RAW264.7 cells, and possessed the ability of pro- and anti-inflammation the cells. RNA sequencing analysis showed that macrophage activation involved Toll-like receptors and mitogen-activated protein kinases pathways. Furthermore, qRT-PCR indicated that phosphoinositide 3 kinase inhibitor LY294002 blocked the mRNA levels of MCP-1, MEK1/2 inhibitor U0126 reduced the mRNA levels of TNF-α and MCP-1, and JNK inhibitor SP600125 prevented the up-regulation of iNOS mRNA in the rFIP-glu-induced cells. FIP-glu mediated these inflammatory effects not through a general pathway, instead through a different pathway for different inflammatory mediator. These data indicate the possibility that rFIP-glu has an important immune-regulation function and thus has potential therapeutic uses.

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The pentacyclic triterpene Lupeol switches M1 macrophages to M2 and ameliorates experimental inflammatory bowel disease

Cited by 119 publications

References 49 publications

Chemopreventive Effects of Phytochemicals and Medicines on M1/M2 Polarized Macrophage Role in Inflammation-Related Diseases

Chemopreventive Effects of Phytochemicals and Medicines on M1/M2 Polarized Macrophage Role in Inflammation-Related Diseases

Crohn’s Disease Patients with Depression Exhibit Alterations in Monocyte/Macrophage Phenotype and Increased Proinflammatory Cytokine Production

Immunomodulatory activity of Ganoderma lucidum immunomodulatory protein via PI3K/Akt and MAPK signaling pathways in macrophage RAW264.7 cells

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