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Histamine deficiency promotes inflammation-associated carcinogenesis through reduced myeloid maturation and accumulation of CD11b(+)Ly6G(+) immature myeloid cells
Histidine decarboxylase (HDC), the unique enzyme responsible for histamine generation, is highly expressed in myeloid cells but its function is poorly understood. Here, we show that Hdc knockout mice exhibit a markedly increased rate of colon and skin carcinogenesis. Using Hdc-EGFP BAC transgenic mi...
Autores principales: | , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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2010
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3075560/ https://www.ncbi.nlm.nih.gov/pubmed/21170045 http://dx.doi.org/10.1038/nm.2278 |
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author | Yang, Xiang Dong Ai, Walden Asfaha, Samuel Bhagat, Govind Friedman, Richard A. Jin, Guangchun Park, Heuijoon Shykind, Benjamin Diacovo, Thomas G Falus, Andras Wang, Timothy C |
author_facet | Yang, Xiang Dong Ai, Walden Asfaha, Samuel Bhagat, Govind Friedman, Richard A. Jin, Guangchun Park, Heuijoon Shykind, Benjamin Diacovo, Thomas G Falus, Andras Wang, Timothy C |
author_sort | Yang, Xiang Dong |
collection | PubMed |
description | Histidine decarboxylase (HDC), the unique enzyme responsible for histamine generation, is highly expressed in myeloid cells but its function is poorly understood. Here, we show that Hdc knockout mice exhibit a markedly increased rate of colon and skin carcinogenesis. Using Hdc-EGFP BAC transgenic mice, we demonstrate that Hdc is expressed primarily in CD11b(+)Ly6G(+) immature myeloid cells (IMCs) that are recruited early on in chemical carcinogenesis. Transplant of Hdc-deficient bone marrow to wildtype recipients results in increased CD11b(+)Ly6G(+) cell mobilization and reproduces the cancer susceptibility phenotype. In addition, IMCs from Hdc knockout mice promote the growth of cancer xenografts and colon cancer cells downregulate Hdc expression through promoter hypermethylation and inhibits myeloid cell maturation. Exogenous histamine induces the differentiation of IMCs and suppresses their ability to support the growth of xenografts. These data indicate key roles for Hdc and histamine in myeloid cell differentiation, and CD11b(+)Ly6G(+) IMCs in early cancer development. |
format | Text |
id | pubmed-3075560 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
record_format | MEDLINE/PubMed |
spelling | pubmed-30755602011-07-01 Histamine deficiency promotes inflammation-associated carcinogenesis through reduced myeloid maturation and accumulation of CD11b(+)Ly6G(+) immature myeloid cells Yang, Xiang Dong Ai, Walden Asfaha, Samuel Bhagat, Govind Friedman, Richard A. Jin, Guangchun Park, Heuijoon Shykind, Benjamin Diacovo, Thomas G Falus, Andras Wang, Timothy C Nat Med Article Histidine decarboxylase (HDC), the unique enzyme responsible for histamine generation, is highly expressed in myeloid cells but its function is poorly understood. Here, we show that Hdc knockout mice exhibit a markedly increased rate of colon and skin carcinogenesis. Using Hdc-EGFP BAC transgenic mice, we demonstrate that Hdc is expressed primarily in CD11b(+)Ly6G(+) immature myeloid cells (IMCs) that are recruited early on in chemical carcinogenesis. Transplant of Hdc-deficient bone marrow to wildtype recipients results in increased CD11b(+)Ly6G(+) cell mobilization and reproduces the cancer susceptibility phenotype. In addition, IMCs from Hdc knockout mice promote the growth of cancer xenografts and colon cancer cells downregulate Hdc expression through promoter hypermethylation and inhibits myeloid cell maturation. Exogenous histamine induces the differentiation of IMCs and suppresses their ability to support the growth of xenografts. These data indicate key roles for Hdc and histamine in myeloid cell differentiation, and CD11b(+)Ly6G(+) IMCs in early cancer development. 2010-12-19 2011-01 /pmc/articles/PMC3075560/ /pubmed/21170045 http://dx.doi.org/10.1038/nm.2278 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Yang, Xiang Dong Ai, Walden Asfaha, Samuel Bhagat, Govind Friedman, Richard A. Jin, Guangchun Park, Heuijoon Shykind, Benjamin Diacovo, Thomas G Falus, Andras Wang, Timothy C Histamine deficiency promotes inflammation-associated carcinogenesis through reduced myeloid maturation and accumulation of CD11b(+)Ly6G(+) immature myeloid cells |
title | Histamine deficiency promotes inflammation-associated carcinogenesis through reduced myeloid maturation and accumulation of CD11b(+)Ly6G(+) immature myeloid cells |
title_full | Histamine deficiency promotes inflammation-associated carcinogenesis through reduced myeloid maturation and accumulation of CD11b(+)Ly6G(+) immature myeloid cells |
title_fullStr | Histamine deficiency promotes inflammation-associated carcinogenesis through reduced myeloid maturation and accumulation of CD11b(+)Ly6G(+) immature myeloid cells |
title_full_unstemmed | Histamine deficiency promotes inflammation-associated carcinogenesis through reduced myeloid maturation and accumulation of CD11b(+)Ly6G(+) immature myeloid cells |
title_short | Histamine deficiency promotes inflammation-associated carcinogenesis through reduced myeloid maturation and accumulation of CD11b(+)Ly6G(+) immature myeloid cells |
title_sort | histamine deficiency promotes inflammation-associated carcinogenesis through reduced myeloid maturation and accumulation of cd11b(+)ly6g(+) immature myeloid cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3075560/ https://www.ncbi.nlm.nih.gov/pubmed/21170045 http://dx.doi.org/10.1038/nm.2278 |
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