BCG immunotherapy inhibits cancer progression by promoting the M1 macrophage differentiation of THP‑1 cells via the Rb/E2F1 pathway in cervical carcinoma

Lung cancer is a most common cancer worldwide. Tumor-associated macrophage (TAM) is known a key effector cell in tumor microenvironment. Meanwhile, STAT6 is crucial to cancer development. We aimed to determine the interaction between STAT6 and TAMs in lung cancer. In this work, firstly, we established mouse model of lung cancer. Then, immunofluorescence was performed to determine STAT6 and CD206 level in lung cancer tissue and adjacent normal tissues as well as model mice. RT-qPCR was applied to detect differentiation of macrophage and determine related gene expression. After treatment of siRNA of STAT6 or STAT6 inhibitor (AS1517499), Transwell assay and MTT were used to determine cell proliferation and migration. STAT6 was upregulated in lung cancer tissues while arginase was more active in M2 macrophage rather than M1 macrophage. Transfection of si-STAT6 not only decreased differentiation in M2 macrophage but also inhibited proliferative, migratory and invasive ability of cancer cells while AS1517499 led to reduced tumor growth. STAT6 inhibition caused decreased expression of M2 macrophages. Similarly, intratumoral T cell markers showed that CD8+T cell gene expression and CD4-mediated T cell marker FoxP3 was increased slightly. Taken altogether, macrophage-STAT6 promotes cell migration and proliferation in lung cancer.

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Interleukin 26 Skews Macrophage Polarization Towards M1 Phenotype by Activating cJUN and the NF-κB Pathway

Cells ◽

10.3390/cells9040938 ◽

2020 ◽

Vol 9 (4) ◽

pp. 938

Author(s):

Yi-Hsuan Lin ◽

Yi-Hsun Wang ◽

Yi-Jen Peng ◽

Feng-Cheng Liu ◽

Gu-Jiun Lin ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Messenger Rna ◽

Molecular Mechanisms ◽

Macrophage Polarization ◽

Enzyme Linked Immunosorbent Assay ◽

M2 Macrophage ◽

Macrophage Differentiation ◽

Macrophage Cells ◽

M1 Macrophage ◽

Interleukin 26

Interleukin 26 (IL-26) is a new member of the IL-10 family that is highly expressed in rheumatoid arthritis (RA). However, the functions of IL-26 produced by macrophages in RA have not been elucidated. In the present work, we evaluated the effects and the mechanisms of IL-26 on M1 and M2 macrophage differentiation. Human or mouse macrophage cells were treated with lipopolysaccharides (LPS), interferon gamma (IFNγ), or IL-4 alone or concurrently treated with IL-26 to monitor M1 or M2 macrophage subtypes. The expression level of M1 or M2 macrophage genes was evaluated by reverse transcription polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). The molecular mechanisms of downstream signaling activation during differentiation were investigated by immunoblotting assay. Our results found that IL-26 promoted macrophage cells from CD80+ M1 macrophage differentiation, not from the CD206+ M2 phenotype. The messenger RNA of M1-type macrophage markers tumor necrosis factor alpha (TNFα) and inducible nitric oxide synthase (iNOS) was up-regulated in the IL-26-treated group. Also, the M1-related proinflammatory cytokines TNFα and IL-6 were induced after IL-26 stimulation. Interestingly, IL-10, a cytokine marker of M2 macrophage, was also elevated after IL-26 stimulation. Moreover, the M1-like macrophage stimulated by IL-26 underwent cJUN, nuclear factor kappa B (NF-κB), and signal transducer and activator of transcription 1 (STAT1) activation. Our findings suggested the role of IL-26 in synovial macrophages of active rheumatoid arthritis and provided a new insight into IL-26 as a candidate therapeutic target in rheumatoid arthritis.

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Interleukin‐5 deletion promotes sepsis‐induced M1 macrophage differentiation, deteriorates cardiac dysfunction, and exacerbates cardiac injury via the NF‐κB p65 pathway in mice

BioFactors ◽

10.1002/biof.1681 ◽

2020 ◽

Vol 46 (6) ◽

pp. 1006-1017

Author(s):

Wanqian Liang ◽

Jianhua Li ◽

Caiyan Bai ◽

Yingen Chen ◽

Yan Li ◽

...

Keyword(s):

Cardiac Dysfunction ◽

Cardiac Injury ◽

Macrophage Differentiation ◽

Interleukin 5 ◽

M1 Macrophage

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The Use of Cisplatin to Treat Advanced-Stage Cervical Cancer During Pregnancy Allows Fetal Development and Prevents Cancer Progression: Report of a Case and Review of the Literature

International Journal of Gynecological Cancer ◽

10.1111/igc.0b013e31819bcff8 ◽

2009 ◽

Vol 19 (2) ◽

pp. 273-276 ◽

Cited By ~ 27

Author(s):

Angela Boyd ◽

Valerie Cowie ◽

Charlie Gourley

Keyword(s):

Cervical Cancer ◽

Cancer Progression ◽

Cervical Carcinoma ◽

Fetal Development ◽

Clear Cell ◽

Advanced Disease ◽

Early Stage ◽

Third Trimester ◽

Early Stage Disease ◽

Stage Disease

Background:Cervical cancer is one of the most frequently encountered malignancies in pregnancy. For early-stage disease arising in late second/third trimester, treatment may be delayed until delivery. However, in advanced disease, data are lacking.Case:A 26-year-old woman presented at 21 weeks gestation with a stage IIB high-grade clear cell cervical carcinoma. At 25 + 1 weeks gestation, cisplatin 100 mg/m2 every 21 days was commenced. One month after cycle 3, a healthy infant was delivered. Thereafter, further cisplatin, intracavity cesium, and chemoradiation were administered. Findings from subsequent clinical examination and magnetic resonance imaging were normal. Fifteen months post treatment, both patient and baby remain well.Conclusion:Neoadjuvant cisplatin chemotherapy can be used in stage IIB cervical carcinoma during pregnancy to allow fetal development and prevent disease progression before delivery.

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Assessment of the Expression of Long Noncoding Mitochondrial RNAs (lncmtRNAs) During Cervical Cancer Progression and Cervical Carcinoma

Journal of Cancer Science & Therapy ◽

10.4172/1948-5956.1000386 ◽

2016 ◽

Vol 08 (02) ◽

Cited By ~ 3

Author(s):

Komal Dadlani ◽

Constanza Lopez

Keyword(s):

Cervical Cancer ◽

Cancer Progression ◽

Cervical Carcinoma

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Interleukin-18 Expression Increases in the Aorta and Plasma of Patients with Acute Aortic Dissection

Mediators of Inflammation ◽

10.1155/2019/8691294 ◽

2019 ◽

Vol 2019 ◽

pp. 1-10 ◽

Cited By ~ 2

Author(s):

Haiying Hu ◽

Guangtai Zhang ◽

Huanli Hu ◽

Wenjing Liu ◽

Jixiang Liu ◽

...

Keyword(s):

Aortic Dissection ◽

Acute Aortic Dissection ◽

Linear Regression Analysis ◽

Human Aorta ◽

Interleukin 18 ◽

Macrophage Differentiation ◽

Vascular Smcs ◽

M1 Macrophage ◽

Underlying Mechanisms

Background. Interleukin- (IL-) 18 is a proinflammatory cytokine related to cardiovascular diseases, including hypertension and atherosclerosis. This study is aimed at determining whether IL-18 is related to aortic dissection (AD) and identifying the underlying mechanisms. Methods. IL-18 expression in human aorta samples from AD (n=8) and non-AD (NAD, n=7) patients was measured. In addition, the IL-18, IL-6, interferon- (IFN-) γ, and IL-18-binding protein (IL-18BP) concentrations in plasma samples collected from the NAD and AD patients were detected. The effects of IL-18 on macrophage differentiation and smooth muscle cell (SMC) apoptosis were investigated in vitro. Results. IL-18 expression was significantly increased in the aorta samples from the AD patients compared with those from the NAD patients, especially in the torn section. Aortic IL-18 was mainly derived from macrophages and also partly derived from CD4+ T lymphocytes and vascular SMCs. Plasma IL-18, IFN-γ, and IL-6 levels were significantly higher in the AD group than in the NAD group, and the IL-18 levels were positively correlated with the IFN-γ and IL-6 levels. In addition, plasma IL-18BP and free IL-18 levels were also elevated in the AD group. Linear regression analysis showed that the IL-18 level was independently associated with the presence of AD. In addition, anti-mouse IL-18-neutralizing monoclonal antibodies (anti-IL-18 nAb) inhibited angiotensin II-induced M1 macrophage differentiation and SMC apoptosis in vitro. Conclusion. IL-18 may participate in AD by regulating macrophage differentiation and macrophage-induced SMC apoptosis.

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Overexpression of FUBP1 is associated with human cervical carcinoma development and prognosis

10.21203/rs.3.rs-95042/v1 ◽

2020 ◽

Author(s):

Haofan Yin ◽

Zhijian Huang ◽

Zhikun Wu ◽

Xuepin Lin ◽

Chunguang Di ◽

...

Keyword(s):

Cancer Progression ◽

Cervical Carcinoma ◽

Disease Free Survival ◽

Enrichment Analysis ◽

Gene Set Enrichment Analysis ◽

Signal Pathways ◽

Protein Levels ◽

Ppi Networks ◽

T Classification

Abstract Background: Far upstream element-binding protein 1 (FUBP1) has been shown to involve in the tumorigenesis and tumor progression of various cancers. However, the expression and function of FUBP1 in cervical carcinoma remains unknown.Methods: Transcriptional expression of FUBP1 was initially evaluated using the Oncomine database, followed by evaluation of FUBP1 protein levels using immunohistochemistry in 119 cervical carcinoma patient tissues. In vitro experiments were performed to assess the tumorigenic role of FUBP1. Besides, Gene Set Enrichment Analysis, EnrichmentMap analysis, and protein-protein interaction (PPI) networks were used to evaluate the potential mechanisms of FUBP1 in promoting cervical cancer progression.Results: In this research, we found both FUBP1 mRNA transcription and protein expression levels increased significantly in cervical carcinoma tissues compared with adjacent normal cervical tissues. Furthermore, elevated FUBP1 expression was positively correlated with age, T classification, N classification, tumor recurrence, Ki67 expression, and poor prognosis in cervical carcinoma patients. Besides, elevated FUBP1 expression acted as an independent unfavorable predictor for overall survival and disease-free survival in cervical carcinoma. Overexpression of FUBP1 significantly promoted cervical carcinoma cell proliferation and inhibits cell apoptosis in vitro, while knockdown of FUBP1 showed the opposite effect. Mechanistically, bioinformatics analysis revealed that FUBP1 promoted the biological function of cervical carcinoma cells via enhancing DNA repair signal pathways. Conclusions: our results demonstrate for the first time that FUBP1 is a novel prognostic factor and therapeutic target for cervical carcinoma.

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Anti-Interleukin-16-Neutralizing Antibody Attenuates Cardiac Inflammation and Protects against Cardiac Injury in Doxorubicin-Treated Mice

Mediators of Inflammation ◽

10.1155/2021/6611085 ◽

2021 ◽

Vol 2021 ◽

pp. 1-10

Author(s):

Jianwei Zhang ◽

Zicong Yang ◽

Zhishan Liang ◽

Mengjie Wang ◽

Changxing Hu ◽

...

Keyword(s):

Troponin T ◽

Cardiac Injury ◽

Neutralizing Antibody ◽

Serum Levels ◽

Cardiomyocyte Apoptosis ◽

Macrophage Differentiation ◽

Cardiac Inflammation ◽

Pathway Activation ◽

M1 Macrophage

Background. Interleukin-16 (IL-16) is an important inflammatory regulator and has been shown to have a powerful effect on the regulation of the inflammatory response. Cardiac inflammation has been reported to be closely related to doxorubicin- (DOX-) induced cardiac injury. In this study, the role of IL-16 in DOX-induced cardiac injury and the possible mechanisms were examined. Methods. Cardiac IL-16 levels were first measured in DOX- or saline-treated mice. Additionally, mice were pretreated with the anti-IL-16-neutralizing antibody (nAb) or isotype IgG for 1 day and further administered DOX or saline for 5 days. Then, cardiac injury, cardiac M1 macrophage levels, and cardiomyocyte apoptosis were analyzed. The effects of the anti-IL-16 nAb on macrophage differentiation and cardiomyocyte apoptosis were also investigated in vitro. Results. DOX administration increased IL-16 expression in cardiac macrophages compared with that of saline treatment. The anti-IL-16 nAb significantly decreased serum levels of lactate dehydrogenase (LDH), myocardial-bound creatine kinase (CK-MB), and cardiac troponin T (cTnT) and elevated cardiac function in DOX-induced mice. Treatment with the anti-IL-16 nAb also reduced p65 pathway activation, decreased M1 macrophage-related marker and cytokine expression, and protected against cardiomyocyte apoptosis in DOX-induced mice. In cell studies, the anti-IL-16 nAb also reduced DOX-induced M1 macrophage differentiation and alleviated apoptosis in cardiomyocytes cocultured with macrophages. Conclusions. The anti-IL-16 nAb protects against DOX-induced cardiac injury by reducing cardiac inflammation, and IL-16 may be a promising target to prevent DOX-related cardiac injury.

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Macrophage Differentiation from Monocytes Is Influenced by the Lipid Oxidation Degree of Low Density Lipoprotein

Mediators of Inflammation ◽

10.1155/2015/235797 ◽

2015 ◽

Vol 2015 ◽

pp. 1-10 ◽

Cited By ~ 17

Author(s):

Jin-Won Seo ◽

Eun-Jeong Yang ◽

Kyung-Hwa Yoo ◽

In-Hong Choi

Keyword(s):

Lipid Oxidation ◽

Oxidized Ldl ◽

Mannose Receptor ◽

Receptor Expression ◽

Supporting Evidence ◽

M2 Macrophages ◽

Macrophage Phenotype ◽

Macrophage Differentiation ◽

Oxidation Degree ◽

M1 Macrophage

LDL plays an important role in atherosclerotic plaque formation and macrophage differentiation. However, there is no report regarding the oxidation degree of LDL and macrophage differentiation. Our study has shown that the differentiation into M1 or M2 macrophages is related to the lipid oxidation level of LDL. Based on the level of lipid peroxidation, LDL is classified into high-oxidized LDL (hi-oxLDL) and low-oxidized LDL (low-oxLDL). The differentiation profiles of macrophages were determined by surface receptor expression and cytokine secretion profiles. Low-oxLDL induced CD86 expression and production of TNF-αand IL-12p40 in THP-1 cells, indicating an M1 macrophage phenotype. Hi-oxLDL induced mannose receptor expression and production of IL-6 and monocyte chemoattractant protein-1, which mostly match the phenotype of M2 macrophages. Further supporting evidence for an M2 polarization by hi-oxLDL was the induction of LOX-1 in THP-1 cells treated with hi-oxLDL but not with low-oxLDL. Similar results were obtained in primary human monocytes. Therefore, our results strongly suggest that the oxidation degree of LDL influences the differentiation of monocytes into M1 or M2 macrophages and determines the inflammatory fate in early stages of atherosclerosis.

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