Cytotherapy with M1-polarized macrophages ameliorates liver fibrosis by modulating immune microenvironment in mice

Ma, Ping; Gao, Chun-Chen; Yi, Jun; Zhao, Junlong; Liang, Shi-Qian; Zhao, Yang; Ye, Yuchen; Bai, Jian; Zheng, Qijun; Dou, Kefeng; Han, Hua; Qin, Hong‐Yan

doi:10.1016/j.jhep.2017.05.022

Cited by 203 publications

(166 citation statements)

References 38 publications

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“…A remarkable reduction in α-SMA (alpha-smooth muscle actin) and desmin indicated a decrement in the activated number of hepatic stellate cells (HSCs), and TUNEL-positive marker accompanied with an increased number of NK cells suggested that the decrement was due to apoptosis of HSCs (but not hepatocytes) after tail vein infusion of M φ and M1 polarized macrophages. Another novel finding of this study was a new classification of restorative macrophage with Ly6c expression that was recruited by M1 and M φ , which is responsible for anti-fibrosis and hepatocyte proliferation improvement effects [33]. It has been reported that polarized macrophages also play important roles in fibrosis of different organs including kidney and cardiovascular systems, suggesting the importance of maintaining the balance of M1/M2 polarization to avoid the occurrence of pro-fibrotic events [63,64,65].…”

Section: Role Of Macrophages In Liver Protectionmentioning

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 Liver Protectionmentioning

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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“…Six-week-old C57BL/6 mice were used in all experiments and were purchased from Shanghai Shanhai Laboratory Animal Center (Shanghai, China). All mice underwent BDL, which was previously described (15,16). The test group was injected by intraperitoneal route every 3 d with 25 mg/g SB216763 (Sigma-Adrich, Shanghai, China) diluted in DMSO; the first injection was performed 2 h prior to surgery.…”

Section: Animals and Surgerymentioning

confidence: 99%

Inhibition of GSK‐3β induces AP‐1‐mediated osteopontin expression to promote cholestatic liver fibrosis

Zhuang

Hua

et al. 2018

FASEB j.

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The contribution of glycogen synthase kinase-3β (GSK-3β) to cholestatic liver disease (CLD) remains unknown. We investigated the role and mechanism of GSK-3β in vivo in liver tissues of patients with CLD and the bile duct ligation (BDL) mouse model and in vitro using a hepatic progenitor cell (HPC) and hepatic stellate cell (HSC) coculture system. In liver tissues of patients with CLD, expression of the inactive form of GSK-3β, phospho-GSK-3β(Ser9), was increased in HPCs. GSK-3β inhibition by SB216763 treatment aggravated liver fibrosis and elevated the expression of osteopontin (OPN) in the BDL mouse model. OPN was significantly overexpressed in liver tissues and serum from patients with CLD. In an HPC and HSC coculture system, inhibition of GSK-3β induced OPN production, which activated HSCs in a cholestatic environment. The expression of activator protein 1 (AP-1), an important downstream transcription factor of GSK-3β, was significantly increased in liver tissues of patients with CLD and SB216763-treated BDL mice. Finally, OPN expression was directly modulated by AP-1. These observations indicate that GSK-3β inhibition up-regulates OPN expression via AP-1 activation, which accelerates the progression of cholestatic liver fibrosis in patients with CLD and in BDL mice.-Zhuang, S., Hua, X., He, K., Zhou, T., Zhang, J., Wu, H., Ma, X., Xia, Q., Zhang, J. Inhibition of GSK-3β induces AP-1-mediated osteopontin expression to promote cholestatic liver fibrosis.

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“…Classically activated macrophages (M1) play a major role in defense against bacteria and viruses by activating inflammatory signaling pathways through secreting pro-inflammatory cytokines (IFNγ, IL-1, IL-6, IL-12, IL-23, and TNFα) (10). Alternatively activated macrophages (M2) are activated by IL-4 and IL-13 and participate in tissue remodeling and fibrosis by regulation of anti-inflammatory response signal production through secreting IL-10 and TGF-β (11,12). M2/M1 macrophage polarization is essential for maintaining macrophage phagocytosis and immune function (13,14).…”

Section: Introductionmentioning

confidence: 99%

SHIP-1 Regulates Phagocytosis and M2 Polarization Through the PI3K/Akt–STAT5–Trib1 Circuit in Pseudomonas aeruginosa Infection

Qin

Zhou

et al. 2020

Front. Immunol.

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SHIP-1 is an inositol phosphatase that hydrolyzes phosphatidylinositol 3-kinase (PI3K) products and negatively regulates protein kinase B (Akt) activity, thereby modulating a variety of cellular processes in mammals. However, the role of SHIP-1 in bacterial-induced sepsis is largely unknown. Here, we show that SHIP-1 regulates inflammatory responses during Gram-negative bacterium Pseudomonas aeruginosa infection. We found that infected-SHIP-1 −/− mice exhibited decreased survival rates, increased inflammatory responses, and susceptibility owing to elevated expression of PI3K than wild-type (WT) mice. Inhibiting SHIP-1 via siRNA silencing resulted in lipid raft aggregates, aggravated oxidative damage, and bacterial burden in macrophages after PAO1 infection. Mechanistically, SHIP-1 deficiency augmented phosphorylation of PI3K and nuclear transcription of signal transducer and activator of transcription 5 (STAT5) to induce the expression of Trib1, which is critical for differentiation of M2 but not M1 macrophages. These findings reveal a previously unrecognized role of SHIP-1 in inflammatory responses and macrophage homeostasis during P. aeruginosa infection through a PI3K/Akt-STAT5-Trib1 axis.

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Cytotherapy with M1-polarized macrophages ameliorates liver fibrosis by modulating immune microenvironment in mice

Cited by 203 publications

References 38 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

Inhibition of GSK‐3β induces AP‐1‐mediated osteopontin expression to promote cholestatic liver fibrosis

SHIP-1 Regulates Phagocytosis and M2 Polarization Through the PI3K/Akt–STAT5–Trib1 Circuit in Pseudomonas aeruginosa Infection

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