{
    "abstract": "We previously showed that histamine suppressed inflammation-associated colonic tumorigenesis through histamine type 2 receptor (H2R) signaling in mice. This study aimed to precisely elucidate the downstream effects of H2R activation in innate immune cells.\nAnalyses using online databases of single-cell RNA sequencing of intestinal epithelial cells in mice and RNA sequencing of mouse immune cells were performed to determine the relative abundances of 4 histamine receptors among different cell types. Mouse neutrophils, which expressed greater amounts of H2R, were collected from the peritoneum of wild-type and H2R-deficient mice, of which low-density and high-density neutrophils were extracted by centrifugation and were subjected to RNA sequencing. The effects of H2R activation on neutrophil differentiation and its functions in colitis and inflammation-associated colon tumors were investigated in a mouse model of dextran sulfate sodium-induced colitis.\nData analysis of RNA sequencing and quantitative reverse-transcription polymerase chain reaction showed that Hrh2 is highly expressed in neutrophils, but barely detectable in intestinal epithelial cells. In mice, the absence of H2R activation promoted infiltration of neutrophils into both sites of inflammation and colonic tumors. H2R-deficient high-density neutrophils yielded proinflammatory features via nuclear factor-\u03baB and mitogen-activated protein kinase signaling pathways, and suppressed T-cell proliferation. On the other hand, low-density neutrophils, which totally lack H2R activation, showed an immature phenotype compared with wild-type low-density neutrophils, with enhanced MYC pathway signaling and reduced expression of the maturation marker Toll-like receptor\u00a04.\nBlocking H2R signaling enhanced proinflammatory responses of mature neutrophils and suppressed neutrophil maturation, leading to accelerated progression of inflammation-associated colonic tumorigenesis.",
    "authors": [
        {
            "affiliation": "Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas; Department of Pathology, Texas Children's Hospital, Houston, Texas.",
            "firstname": "Zhongcheng",
            "initials": "Z",
            "lastname": "Shi"
        },
        {
            "affiliation": "Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas; Department of Pathology, Texas Children's Hospital, Houston, Texas.",
            "firstname": "Yuko",
            "initials": "Y",
            "lastname": "Mori-Akiyama"
        },
        {
            "affiliation": "Department of Cancer Biology, University of Cincinnati College of Medicine, Cincinnati, Ohio.",
            "firstname": "Wa",
            "initials": "W",
            "lastname": "Du"
        },
        {
            "affiliation": "Department of Neuroscience, Cell Biology and Anatomy, University of Texas Medical Branch, Galveston, Texas.",
            "firstname": "Robert",
            "initials": "R",
            "lastname": "Fultz"
        },
        {
            "affiliation": "Department of Pediatrics, Texas Children's Cancer Center, Houston, Texas.",
            "firstname": "Yanling",
            "initials": "Y",
            "lastname": "Zhao"
        },
        {
            "affiliation": "Department of Pediatrics, Baylor College of Medicine, Houston, Texas; Section of Gastroenterology, Hepatology, and Nutrition, Texas Children's Hospital, Houston, Texas.",
            "firstname": "Wenly",
            "initials": "W",
            "lastname": "Ruan"
        },
        {
            "affiliation": "Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas; Department of Pathology, Texas Children's Hospital, Houston, Texas.",
            "firstname": "Susan",
            "initials": "S",
            "lastname": "Venable"
        },
        {
            "affiliation": "Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas; Department of Pathology, Texas Children's Hospital, Houston, Texas.",
            "firstname": "Melinda A",
            "initials": "MA",
            "lastname": "Engevik"
        },
        {
            "affiliation": "Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas; Department of Pediatrics, Baylor College of Medicine, Houston, Texas; Department of Pathology, Texas Children's Hospital, Houston, Texas. Electronic address: jamesv@bcm.edu.",
            "firstname": "James",
            "initials": "J",
            "lastname": "Versalovic"
        }
    ],
    "conclusions": null,
    "copyrights": "Copyright \u00a9 2022 The Authors. Published by Elsevier Inc. All rights reserved.",
    "doi": "10.1016/j.jcmgh.2021.11.003",
    "journal": "Cellular and molecular gastroenterology and hepatology",
    "keywords": [
        "Cimetidine",
        "Colorectal Cancer",
        "Histamine",
        "Inflammation"
    ],
    "methods": null,
    "publication_date": "2021-11-16",
    "pubmed_id": "34781022\n30224900\n26670383\n30462522\n21170045\n18832739\n29956819\n20028852\n24626392\n31756785\n32198140\n17767165\n31620141\n30315349\n6102784\n14744809\n12950678\n18461651\n21530747\n28690492\n11729120\n27246043\n29492219\n31160207\n27282249\n11406548\n28191674\n29436479\n29198940\n15067010\n26296979\n27610713\n31843598\n16315874\n22670722\n28288458\n2599442\n6405946\n19025815\n22895966\n17880537\n2311886\n24244446\n14597578\n29991641\n20420949\n18521188\n19487293\n31369218\n28569761\n26237011\n28751424",
    "results": "Data analysis of RNA sequencing and quantitative reverse-transcription polymerase chain reaction showed that Hrh2 is highly expressed in neutrophils, but barely detectable in intestinal epithelial cells. In mice, the absence of H2R activation promoted infiltration of neutrophils into both sites of inflammation and colonic tumors. H2R-deficient high-density neutrophils yielded proinflammatory features via nuclear factor-\u03baB and mitogen-activated protein kinase signaling pathways, and suppressed T-cell proliferation. On the other hand, low-density neutrophils, which totally lack H2R activation, showed an immature phenotype compared with wild-type low-density neutrophils, with enhanced MYC pathway signaling and reduced expression of the maturation marker Toll-like receptor\u00a04.",
    "title": "Loss of H2R Signaling Disrupts Neutrophil Homeostasis and Promotes Inflammation-Associated Colonic Tumorigenesis in Mice.",
    "xml": "<Element 'PubmedArticle' at 0x788505084360>"
}