Neutrophils, Nitric Oxide Synthase, and Mutations in the Mutatect Murine Tumor Model

Sandhu, Jagdeep K.; Privora, Helen; Wenckebach, Georg F. C.; Birnboim, H.C.

doi:10.1016/s0002-9440(10)64755-4

Cited by 83 publications

(66 citation statements)

References 48 publications

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“…Activated STAT3 is the main regulator of IL‐6 in MDSCs, inducing cell survival, cell proliferation (Xin et al ., 2009), and immunosuppressive activity (Kujawski et al ., 2008). IL‐8 also enhances PMN‐MDSC infiltration into tumor tissues (Kumar et al ., 2016; Sandhu et al ., 2000). Furthermore, IL‐1β is reported to induce the accumulation of MDSCs (Bunt et al ., 2007; Elkabets et al ., 2010).…”

Section: Discussionmentioning

confidence: 99%

ZEB1‐regulated inflammatory phenotype in breast cancer cells

et al. 2017

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Zinc finger E‐box binding protein 1 (ZEB1) and ZEB2 induce epithelial‐mesenchymal transition (EMT) and enhance cancer progression. However, the global view of transcriptional regulation by ZEB1 and ZEB2 is yet to be elucidated. Here, we identified a ZEB1‐regulated inflammatory phenotype in breast cancer cells using chromatin immunoprecipitation sequencing and RNA sequencing, followed by gene set enrichment analysis (GSEA) of ZEB1‐bound genes. Knockdown of ZEB1 and/or ZEB2 resulted in the downregulation of genes encoding inflammatory cytokines related to poor prognosis in patients with cancer, including IL6 and IL8, therefore suggesting that ZEB1 and ZEB2 have similar functions in terms of the regulation of production of inflammatory cytokines. Antibody array and ELISA experiments confirmed that ZEB1 controlled the production of the IL‐6 and IL‐8 proteins. The secretory proteins regulated by ZEB1 enhanced breast cancer cell proliferation and tumor growth. ZEB1 expression in breast cancer cells also affected the growth of fibroblasts in cell culture, and the accumulation of myeloid‐derived suppressor cells in tumors in vivo. These findings provide insight into the role of ZEB1 in the progression of cancer, mediated by inflammatory cytokines, along with the initiation of EMT.

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Section: Discussionmentioning

confidence: 99%

ZEB1‐regulated inflammatory phenotype in breast cancer cells

et al. 2017

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“…Conversely, one of the major challenges faced by tumor immunologists is the identification of appropriate tumor Ags that are immunogenic because the vast majority of cancer Ags are self and are thus subject to the constraints of tolerance. Recently, nitrotyrosine has been observed in a number of human cancer settings including bladder carcinoma (38), colorectal carcinoma (39), breast cancer (40), esophageal squamous cell carcinoma (41), nonHodgkin's lymphoma (42), lung cancer (43), and melanoma (44) as well as in experimental tumor models (45). If our previous findings regarding the lack of central tolerance against nitrated-PCC in PCC-transgenic mice are a globally applicable phenomenon, then targeting of nitrotyrosine-containing "self" peptides present on tumor cells may be a rational, alternative approach for tumor immunotherapy.…”

Section: Discussionmentioning

confidence: 99%

Conversion of Tyrosine to the Inflammation-Associated Analog 3′-Nitrotyrosine at Either TCR- or MHC-Contact Positions Can Profoundly Affect Recognition of the MHC Class I-Restricted Epitope of Lymphocytic Choriomeningitis Virus Glycoprotein 33 by CD8 T Cells

Hardy

Wick

Webb

2008

The Journal of Immunology

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Immunohistochemical detection of increased levels of protein-associated nitrotyrosine has become widely used as a surrogate marker of in situ inflammation. However, the potential consequences of protein-associated nitrotyrosine formation in terms of cellular immune recognition has received surprisingly little attention. Using a well-defined I-EK-restricted epitope of pigeon cytochrome c, we previously demonstrated that conversion of a single tyrosine residue to nitrotyrosine can have a profound effect on recognition by CD4 T cells. In this study, we used the MHC class I-restricted epitope of lymphocytic choriomeningitis virus glycoprotein (gp33) to demonstrate that conversion of tyrosine to nitrotyrosine can also profoundly affect recognition of MHC class I-restricted epitopes. Conversion of the Y4 residue of the gp33 epitope to nitrotyrosine completely abrogated recognition by gp33-specific T cells from P14 TCR-transgenic mice. In contrast, CD8+ T cells specific for “nitrated gp33” (NY-gp33) can be readily elicited in C57BL/6 mice after immunization with NY-gp33 peptide. Interestingly, T-T hybridomas specific for NY-gp33 peptide were found to fall into two distinct subsets, being specific for NY-gp33 presented in the context of either H-2Db or H-2Kb. This latter result is surprising in light of previous structural studies showing that Y4 comprises a critical TCR-contact residue when presented by H-2Db but that the same residue points downward into the peptide-binding groove of the MHC when presented by H-2Kb. Together, these results indicate that nitrotyrosine formation can impact T cell recognition both directly, through alteration of TCR-contact residues, or indirectly, through alterations in MHC-contact positions.

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“…Some reports describe chemical nitration of histones (30)(31)(32), whereas others demonstrate that nuclear staining for nitrotyrosine by immunohistochemistry is often observed in tissues and in NO-exposed cell cultures (33)(34)(35). Recently, Haqqani et al (36) described that histones are the most prominent nitrated proteins in the Mutatect tumor tissue as well as in the cultured Mutatect cells that are exposed to NO.…”

Section: Discussionmentioning

confidence: 99%

Histone H1.2 is a substrate for denitrase, an activity that reduces nitrotyrosine immunoreactivity in proteins

Irie

Saeki

Kamisaki

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

124

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Several reports have described an activity that modifies nitrotyrosinecontaining proteins and their immunoreactivity to nitrotyrosine Abs. Without knowing the product of the reaction, this new activity has been called a ''denitrase.'' In those studies, some nonspecific proteins, which have multiple tyrosine residues, e.g., albumin, were used as a substrate. Therefore, the studies were based on an unknown mechanism of reaction and potentially a high background. To solve these problems, one of the most important things is to find a more suitable substrate for assay of the enzyme. We developed an assay strategy for determining the substrate for denitrase combining 2D-gel electrophoresis and an on-blot enzyme assay. The resulting substrate from RAW 264.7 cells was Histone H1.2, an isoform protein of linker histone. Histone H1.2 has only one tyrosine residue in the entire molecule, which ensures the exact position of the substrate to be involved. It has been reported that Histones are the most prominent nitrated proteins in cancer tissues. It was also demonstrated that tyrosine nitration of Histone H1 occurs in vivo. These findings lead us to the idea that Histone H1.2 might be an intrinsic substrate for denitrase. We nitrated recombinant and purified Histone H1.2 chemically and subjected it to an on-blot enzyme assay to characterize the activity. Denitrase activity behaved as an enzymatic activity because the reaction was time dependent and was destroyed by heat or trypsin treatment. The activity was shown to be specific for Histone H1.2, to differ from proteasome activity, and to require no additional cofactors.

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Neutrophils, Nitric Oxide Synthase, and Mutations in the Mutatect Murine Tumor Model

Cited by 83 publications

References 48 publications

ZEB1‐regulated inflammatory phenotype in breast cancer cells

ZEB1‐regulated inflammatory phenotype in breast cancer cells

Conversion of Tyrosine to the Inflammation-Associated Analog 3′-Nitrotyrosine at Either TCR- or MHC-Contact Positions Can Profoundly Affect Recognition of the MHC Class I-Restricted Epitope of Lymphocytic Choriomeningitis Virus Glycoprotein 33 by CD8 T Cells

Histone H1.2 is a substrate for denitrase, an activity that reduces nitrotyrosine immunoreactivity in proteins

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