RETRACTED: The M2 macrophages induce autophagic vascular disorder and promote mouse sensitivity to urethane-related lung carcinogenesis

Li, G.-G.; Guo, Zhenzhen; Ma, Xiaofang; Cao, Ning; Geng, Shengnan; Zheng, Yaqiu; Meng, Mingjing; Lin, Hailong; Hân, Gia; Du, Gangjun

doi:10.1016/j.dci.2016.01.010

Cited by 22 publications

(14 citation statements)

References 32 publications

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“…These observations are not surprising as CHQ and ART are known for their antimalarial action through multiple modes on their target, but their mechanism of action as immunomodulators is not clearly elucidated. The M2 phenotype is previously related to abnormal autophagy and angiogenesis (Li et al., ). We speculate that CHQ, a known autophagy inhibitor, may attenuate Hz‐induced M2‐like MO activation by inhibiting autophagy.…”

Section: Discussionmentioning

confidence: 95%

Hemozoin‐induced activation of human monocytes toward M2‐like phenotype is partially reversed by antimalarial drugs—chloroquine and artemisinin

et al. 2018

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Plasmodium falciparum malaria is the most severe form of malaria with several complications. The malaria pigment-hemozoin (Hz) is associated with severe anemia, cytokine dysfunction, and immunosuppression, thus making it an interesting target for developing new strategies for antimalarial therapy. Monocytes (MO) in circulation actively ingest Hz released by Plasmodium parasites and secrete pro- and anti-inflammatory cytokines. M1 and M2 types represent the two major forms of MO/macrophages (MQ) with distinct phenotypes and opposing functions. Imbalance in the polarization of these types is reported in many infectious diseases. Though the association of Hz with immunosuppression is well documented, its role in activation of MO in context of M1/M2 phenotypes remains to be addressed. We report here that natural Hz drives human MO toward M2-like phenotype as evidenced by the expression of M2 signature markers. Hz-fed MO showed elevated transcript and secreted level of IL-10, CCL17, CCL1, expression of mannose-binding lectin receptor (CD206), and arginase activity. Hz attenuated HLA-DR expression, nitric oxide, and reactive oxygen species production, which are the features of M1 phenotype. Our data also implicate the involvement of p38 MAPK, PI3K/AKT, and NF-κB signaling pathways in skewing of Hz-fed MO toward M2-like type and suppression of mitogen-stimulated lymphocyte proliferation. Importantly, antimalarial drugs-chloroquine and artemisinin-partially reversed activation of Hz-induced MO toward M2-like phenotype. Considering the limitations in the current therapeutic options for malaria, we propose that these drugs may be re-examined for their potential as immunomodulators and candidates for adjunctive treatment in malaria.

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Section: Discussionmentioning

confidence: 95%

Hemozoin‐induced activation of human monocytes toward M2‐like phenotype is partially reversed by antimalarial drugs—chloroquine and artemisinin

et al. 2018

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“…CMA is activated as a protective mechanism during chemotherapy, and thus causes the acquired resistance phenotype of some cancer cells [ 12 , 33 ]. Substances secreted by M2-TAMs have been reported to activate autophagy and promote cancer progression and treatment resistance [ 34 ]. Here, we found that M2-TAMs activated CMA, which further reduced apoptosis following oxaliplatin treatment.…”

Section: Discussionmentioning

confidence: 99%

M2 tumor-associated macrophages produce interleukin-17 to suppress oxaliplatin-induced apoptosis in hepatocellular carcinoma

Guo

et al. 2017

Oncotarget

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M2 macrophages are a major component of the tumor microenvironment and are important promoters of tumor occurrence and progression. In this study, we detected large numbers of M2 macrophages in hepatocellular carcinoma tissues using immunohistochemistry and immunofluorescence. Moreover, upon oxaliplatin treatment, the M2 macrophages overexpressed interleukin-17, an important inflammatory cytokine, and thus inhibited oxaliplatin-induced apoptosis. By knocking down the interleukin-17 receptor and lysosome-associated membrane protein 2A (a key protein in chaperone-mediated autophagy) in hepatocellular carcinoma cells, we found that interleukin-17 stimulated chaperone-mediated autophagy, which further suppressed apoptosis upon oxaliplatin treatment. Chaperone-mediated autophagy induced tolerance to oxaliplatin treatment by reducing cyclin D1 expression; thus, cyclin D1 overexpression stimulated oxaliplatin-induced apoptosis. In addition, cyclin D1 expression was inhibited by interleukin-17, but increased when the interleukin-17 receptor was knocked down. Thus M2 macrophages in the hepatocellular carcinoma microenvironment generate large amounts of interleukin-17, which suppress oxaliplatin-induced tumor cell apoptosis by activating chaperone-mediated autophagy and in turn reducing cyclin D1 expression. These findings may facilitate the development of novel therapeutic strategies for chemorefractory liver cancer.

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“…58 Yet, another important role of lysosomes is the removal of dead cell debris to enable resolution of inflammation and tissue remodeling. 61 Interestingly, it has also been shown that CQ attenuates lipopolysaccharideinduced M1 macrophage activation. An M2-to-M1 macrophage transition could be experimentally achieved by CQ at least partially through raising lysosomal pH.…”

Section: Cq Inhibits Lysosomal Acidificationmentioning

confidence: 99%

“…60 Moreover, CQ has the potential to alleviate pathological conditions associated with increased M2 activity, such as vascular disorder during lung carcinogenesis. 61 Interestingly, it has also been shown that CQ attenuates lipopolysaccharideinduced M1 macrophage activation. 62 Dendritic cells also limit lysosomal acidification to optimize antigen processing and allow major histocompatibility complex class I (MHC-I) dependent cross-presentation.…”

Section: Cq Inhibits Lysosomal Acidificationmentioning

confidence: 99%

Dissecting pharmacological effects of chloroquine in cancer treatment: interference with inflammatory signaling pathways

2019

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Chloroquines are 4-aminoquinoline-based drugs mainly used to treat malaria. At pharmacological concentrations, they have significant effects on tissue homeostasis, targeting diverse signaling pathways in mammalian cells. A key target pathway is autophagy, which regulates macromolecule turnover in the cell. In addition to affecting cellular metabolism and bioenergetic flow equilibrium, autophagy plays a pivotal role at the interface between inflammation and cancer progression. Chloroquines consequently have critical effects in tissue metabolic activity and importantly, in key functions of the immune system. In this article, we will review the work addressing the role of chloroquines in the homeostasis of mammalian tissue, and the potential strengths and weaknesses concerning their use in cancer therapy.

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RETRACTED: The M2 macrophages induce autophagic vascular disorder and promote mouse sensitivity to urethane-related lung carcinogenesis

Cited by 22 publications

References 32 publications

Hemozoin‐induced activation of human monocytes toward M2‐like phenotype is partially reversed by antimalarial drugs—chloroquine and artemisinin

Hemozoin‐induced activation of human monocytes toward M2‐like phenotype is partially reversed by antimalarial drugs—chloroquine and artemisinin

M2 tumor-associated macrophages produce interleukin-17 to suppress oxaliplatin-induced apoptosis in hepatocellular carcinoma

Dissecting pharmacological effects of chloroquine in cancer treatment: interference with inflammatory signaling pathways

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