Dataset Information

Cytokine Expression and Macrophage Localization in Xenograft and Allograft Tumor Models Stimulated with Lipopolysaccharide.

ABSTRACT: T cell-deficient mice such as nude mice are often used to generate tumor xenograft for the development of anticancer agents. However, the functionality of the other immune cells including macrophages, dendritic cells (DCs), and myeloid-derived suppressor cells (MDSCs) in the xenograft are largely unknown. Macrophages and dendritic cells (DCs) acquire functionally distinct properties in response to various environmental stimuli; the interaction of these cells with MDSCs in tumor microenvironments regulates cancer progression. Nude mice are less likely to reject human cancer cells because of major histocompatibility complex (MHC) mismatches. The tumor microenvironment in a xenograft, comprising human and mouse cells, exhibits more complex bidirectional signaling and function than that of allograft. Here, we evaluated the differences of myeloid cells between them. Plasma interferon-γ and interleukin-18 concentrations in the xenograft tumor model after lipopolysaccharide (LPS) administration were significantly higher than those in the allograft tumor model. MHC class I, II, and CD80 expression levels were increased in CD11b? and MDSC populations after LPS administration in the spleen of a xenograft tumor model but not in that of an allograft tumor model. Additionally, the number of CD80- and mannose receptor C type 1 (MRC1)-expressing cells was decreased upon LPS administration in the tumor of the xenograft tumor. These results suggest that functions of macrophages and DCs are sustained in the xenograft, whereas their functions in response to LPS were suppressed in the allograft. The findings will encourage the consideration of the effects of myeloid cells in the xenograft for drug development.

SUBMITTER: Masuda J

PROVIDER: S-EPMC5979423 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Cytokine Expression and Macrophage Localization in Xenograft and Allograft Tumor Models Stimulated with Lipopolysaccharide.

Masuda Junko J Shigehiro Tsukasa T Matsumoto Takuma T Satoh Ayano A Mizutani Akifumi A Umemura Chiho C Saito Shoki S Kijihira Mayumi M Takayama Eiji E Seno Akimasa A Murakami Hiroshi H Seno Masaharu M

International journal of molecular sciences 20180423 4

T cell-deficient mice such as nude mice are often used to generate tumor xenograft for the development of anticancer agents. However, the functionality of the other immune cells including macrophages, dendritic cells (DCs), and myeloid-derived suppressor cells (MDSCs) in the xenograft are largely unknown. Macrophages and dendritic cells (DCs) acquire functionally distinct properties in response to various environmental stimuli; the interaction of these cells with MDSCs in tumor microenvironments ...[more]

PMID: 29690614

Similar Datasets

Project description:BackgroundMediated by innate immune cells, inflammation is an underlying presence in the pathogenesis of numerous pulmonary diseases. Macrophages play a critical role in mediating the initial response to infection in the lungs. When there is excessive activation of macrophages, hyper-production of inflammatory factors occurs, with inflammation as the ultimate result. Wogonoside, a bioactive flavonoid glycoside, has been reported to alleviate pulmonary inflammation. However, the mechanism underlying the anti-inflammatory effect of wogonoside has not yet been clarified.MethodsThe productions of nitric oxide (NO) and reactive oxygen species (ROS) were determined using a Griess reagent kit and a DAF-FM DA fluorescent probe, respectively. Moreover, the mRNA levels of inflammatory factors were quantified by qPCR, and the binding ability of c-Jun to promoters of inflammatory factors was performed by ChIP assay. Western blot was employed to detect the protein expression of inflammatory factors and signaling pathway.ResultsIn this study, we found that pre-treatment with wogonoside dramatically suppressed lipopolysaccharide (LPS)-induced increase in the protein and mRNA levels of inflammatory factors in macrophages, such as cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), interleukin (IL)-1β, tumor necrosis factor (TNF)-α, and IL-6. Furthermore, wogonoside profoundly reduced the increase in NO and ROS production and significantly blocked phosphorylation of JNK in LPS-stimulated macrophages. As revealed by Western blot and qPCR analysis, wogonoside mediated the JNK-dependent inhibitory effect. Compared with wogonoside alone, a combination of wogonoside and JNK inhibitor SP600125 provided no extra benefit in suppressing the protein expression and mRNA levels of inflammatory factors in LPS-stimulated macrophages. Additionally, ChIP analysis demonstrated wogonoside to remarkably reduce c-Jun enrichment in COX-2, iNOS, IL-1β, TNF-α, and IL-6 promoters.ConclusionsCollectively, our findings showed that wogonoside notably suppresses LPS-stimulated production of inflammatory factors by repressing the activation of the JNK/c-Jun signaling pathway in macrophages. This suggests that wogonoside could serve as a promising therapeutic agent for pulmonary diseases related to macrophage inflammation.

Dataset Information

Cytokine Expression and Macrophage Localization in Xenograft and Allograft Tumor Models Stimulated with Lipopolysaccharide.

Publications

Cytokine Expression and Macrophage Localization in Xenograft and Allograft Tumor Models Stimulated with Lipopolysaccharide.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets