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Keywords {🔍}

mice, liver, pubmed, hcc, article, google, scholar, cancer, cas, patients, mdr, inflammation, cells, fig, macrophages, inflammatory, monocytes, levels, development, data, response, cell, hepatic, tumor, stat, central, interleukin, hepatocellular, carcinoma, ildeficient, increased, role, model, mouse, chronic, spontaneous, hepatitis, study, kcs, blood, wtil, occurrence, china, expression, circulating, including, tumorigenesis, bone, marrow, higher,

Topics {✒️}

monocyte-derived hepatocyte-stimulating factor monocyte-selective il-6-deficient mice tam-derived il-6-stimulated hepatocytes monocyte-specific il-6-deficient mice il-6-deficient mouse donor article download pdf simulated cardiomyocytes ischemia/reperfusion interleukin-6-type cytokine signalling human monocytes/macrophages/dendritic cells dna-binding factor expressed internal β-actin control hepato-biliary-pancreatic surgery mdr2 p-glycoprotein gene enhancing cell-cycle progression paraffin-embedded liver sections systemic il-6-deficient mouse cre/loxp system il-6-deficient mice exhibited scale bar = 50 μm il-6/stat3 cascade plays fewer f4/80-positive cells hepatocellular carcinoma due macrophage-related cell markers central role played include gadolinium chloride extracellular signal-regulated kinase toxic liver injury interleukin 6/gp130-dependent pathways increased tam-derived il-6 10 ml/kg body weight acute hepatic damage blood leukocyte dna human kupffer cells partially hepatectomized mice yujun shi acute liver damage privacy choices/manage cookies chemical-induced hepatotoxicity progrowth factor required tumor necrosis factor kupffer cells expressing light/dark cycle gp130/jak/stat pathway hepatic acute phase creative commons license serum il-6 level including bcl-xl nat rev cancer il-6/jak/stat3 pathway full access

Questions {❓}

• Autocrine IL-6 signaling: a key event in tumorigenesis?

Schema {🗺️}

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         headline:Deletion of interleukin-6 in monocytes/macrophages suppresses the initiation of hepatocellular carcinoma in mice
         description:Hepatocellular carcinoma (HCC) is associated with inflammation, and roughly 30 % of the global population shows serological evidence of current or past infection with hepatitis B or hepatitis C virus. Resident hepatic macrophages, known as Kupffer cells (KCs), are considered as the specific tumor-associated macrophages (TAMs) of HCC, and can produce various cytokines—most importantly interleukin (IL)-6—to promote tumorigenesis of HCC. However, the roles of KCs and IL-6 in carcinogenesis in the liver are still unclear. We analyzed leukocyte-related peripheral blood data of 192 patients and constructed a mouse model in which the bone marrow was cleared out by irradiation and reconstructed using bone marrow donated from IL-6-deficient mice to further elucidate the hepatic pathological changes in response to toxic challenge and oncogenic gene mutation. Peripheral monocyte counts and serum IL-6 levels were significantly higher in patients with HCC than in those without HCC. In addition, there was a significant difference in the levels of IL-6 among individuals with different histopathological grades. In mice with selective IL-6 ablation in monocytes/KCs, we observed decreased toxic liver injury, inflammatory infiltration, and systemic inflammation. In Mdr2-deficient mice, which spontaneously developed HCC, the loss of IL-6 in monocytes/KCs resulted in inhibition of IL-6/signal transducer and activator of transcription 3 signaling, decreased serum IL-6 levels, and delayed tumorigenesis. Our findings demonstrate that increased TAM-derived IL-6 had an amplifying effect on the inflammation response, thereby promoting the occurrence and development of HCC.
         datePublished:2016-09-02T00:00:00Z
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      headline:Deletion of interleukin-6 in monocytes/macrophages suppresses the initiation of hepatocellular carcinoma in mice
      description:Hepatocellular carcinoma (HCC) is associated with inflammation, and roughly 30 % of the global population shows serological evidence of current or past infection with hepatitis B or hepatitis C virus. Resident hepatic macrophages, known as Kupffer cells (KCs), are considered as the specific tumor-associated macrophages (TAMs) of HCC, and can produce various cytokines—most importantly interleukin (IL)-6—to promote tumorigenesis of HCC. However, the roles of KCs and IL-6 in carcinogenesis in the liver are still unclear. We analyzed leukocyte-related peripheral blood data of 192 patients and constructed a mouse model in which the bone marrow was cleared out by irradiation and reconstructed using bone marrow donated from IL-6-deficient mice to further elucidate the hepatic pathological changes in response to toxic challenge and oncogenic gene mutation. Peripheral monocyte counts and serum IL-6 levels were significantly higher in patients with HCC than in those without HCC. In addition, there was a significant difference in the levels of IL-6 among individuals with different histopathological grades. In mice with selective IL-6 ablation in monocytes/KCs, we observed decreased toxic liver injury, inflammatory infiltration, and systemic inflammation. In Mdr2-deficient mice, which spontaneously developed HCC, the loss of IL-6 in monocytes/KCs resulted in inhibition of IL-6/signal transducer and activator of transcription 3 signaling, decreased serum IL-6 levels, and delayed tumorigenesis. Our findings demonstrate that increased TAM-derived IL-6 had an amplifying effect on the inflammation response, thereby promoting the occurrence and development of HCC.
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      dateModified:2016-09-02T00:00:00Z
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         Interleukin- 6 (IL-6)
         Cancer Research
         Immunology
         Apoptosis
         Oncology
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      name:Laboratory of Pathology, West China Hospital, Sichuan University, Chengdu, China
      name:Key Laboratory of Transplant Engineering and Immunology, Ministry of Health, Chengdu, China
      name:Department of Hepato-Biliary-Pancreatic Surgery, West China Hospital of Sichuan University, Chengdu, China
      name:Department of Hepato-Biliary-Pancreatic Surgery, West China Hospital of Sichuan University, Chengdu, China
      name:Laboratory of Pathology, West China Hospital, Sichuan University, Chengdu, China
      name:Department of Hepato-Biliary-Pancreatic Surgery, West China Hospital of Sichuan University, Chengdu, China

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