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IL-6 influences the polarization of macrophages and the formation and growth of colorectal tumor.

ABSTRACT: Macrophages play a crucial role in tumorigenesis depending upon the phenotype of macrophages found in tumor microenvironments. To date, how the tumor microenvironment affects the phenotypes of macrophages is not yet fully understood. In this study, we constructed a NIH3T3/Src cell line stably overexpresses the Src protein and found that conditioned medium from this cell line was able to induce polarization towards the M2 phenotype in primary bone marrow-derived macrophages (BMDM) and Ana-1 macrophages. Further investigation revealed that IL-6 produced by NIH3T3/Src cells plays a key role in M2 polarization. During the development of colorectal cancer in C57BL/6J-ApcMin/+ mice, increased IL-6 secretion in the interstitial fluid of the colorectal tissues was observed. Furthermore, tumorigenesis in IL-6tm1Kopf mice treated with AOM-DSS, an IL-6 knockout mouse strain, was significantly inhibited compared with the control group, suggesting the important role of IL-6 in promoting tumorigenicity. Our findings identify the target molecules and proinflammatory cytokines responsible for promoting polarization towards the M2 phenotype in macrophages present in tumor microenvironment, which may be useful for the design of novel therapeutic strategies for colorectal cancer.

SUBMITTER: Chen L

PROVIDER: S-EPMC5915127 | biostudies-other | 2018 Apr

REPOSITORIES: biostudies-other

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IL-6 influences the polarization of macrophages and the formation and growth of colorectal tumor.

Chen Lechuang L Wang Shuren S Wang Yu Y Zhang Weina W Ma Kai K Hu Chenfei C Zhu Hongxia H Liang Shufang S Liu Mei M Xu Ningzhi N

Oncotarget 20180403 25

Macrophages play a crucial role in tumorigenesis depending upon the phenotype of macrophages found in tumor microenvironments. To date, how the tumor microenvironment affects the phenotypes of macrophages is not yet fully understood. In this study, we constructed a NIH3T3/Src cell line stably overexpresses the Src protein and found that conditioned medium from this cell line was able to induce polarization towards the M2 phenotype in primary bone marrow-derived macrophages (BMDM) and Ana-1 macro ...[more]

PMID: 29707119

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Project description:BackgroundEbolavirus (EBOV) outbreaks, while sporadic, cause tremendous morbidity and mortality. No therapeutics or vaccines are currently licensed; however, a vaccine has shown promise in clinical trials. A critical step towards development of effective therapeutics is a better understanding of factors that govern host susceptibility to this pathogen. As macrophages are an important cell population targeted during virus replication, we explore the effect of cytokine polarization on macrophage infection.Methods/main findingsWe utilized a BSL2 EBOV model virus, infectious, recombinant vesicular stomatitis virus encoding EBOV glycoprotein (GP) (rVSV/EBOV GP) in place of its native glycoprotein. Macrophages polarized towards a M2-like anti-inflammatory state by combined IL-4 and IL-13 treatment were more susceptible to rVSV/EBOV GP, but not to wild-type VSV (rVSV/G), suggesting that EBOV GP-dependent entry events were enhanced by these cytokines. Examination of RNA expression of known surface receptors that bind and internalize filoviruses demonstrated that IL-4/IL-13 stimulated expression of the C-type lectin receptor DC-SIGN in human macrophages and addition of the competitive inhibitor mannan abrogated IL-4/IL-13 enhanced infection. Two murine DC-SIGN-like family members, SIGNR3 and SIGNR5, were upregulated by IL-4/IL-13 in murine macrophages, but only SIGNR3 enhanced virus infection in a mannan-inhibited manner, suggesting that murine SIGNR3 plays a similar role to human DC-SIGN. In vivo IL-4/IL-13 administration significantly increased virus-mediated mortality in a mouse model and transfer of ex vivo IL-4/IL-13-treated murine peritoneal macrophages into the peritoneal cavity of mice enhanced pathogenesis.SignificanceThese studies highlight the ability of macrophage polarization to influence EBOV GP-dependent virus replication in vivo and ex vivo, with M2a polarization upregulating cell surface receptor expression and thereby enhancing virus replication. Our findings provide an increased understanding of the host factors in macrophages governing susceptibility to filoviruses and identify novel murine receptors mediating EBOV entry.

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IL-6 influences the polarization of macrophages and the formation and growth of colorectal tumor.

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IL-6 influences the polarization of macrophages and the formation and growth of colorectal tumor.

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