Cell mediated immune responses through TLR4 prevents DMBA-induced mammary carcinogenesis in mice

Toll‐like receptors (TLRs) activate signals that are critically involved in the initiation of adaptive immune responses and many tumorigenic chemicals have been associated with activation of those pathways. To determine the role of TLR‐4 (TLR4) in mammary carcinogenesis, we subjected TLR4 deficient...

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Bibliographic Details
Published in:	International journal of cancer Vol. 130; no. 4; pp. 765 - 774
Main Authors:	Naseemuddin, Mohammed, Iqbal, Aneeqa, Nasti, Tahseen H., Ghandhi, Jennifer L., Kapadia, Akash D., Yusuf, Nabiha
Format:	Journal Article
Language:	English
Published:	Hoboken Wiley Subscription Services, Inc., A Wiley Company 15-02-2012 Wiley-Blackwell Wiley Subscription Services, Inc
Subjects:	12-dimethylbenz(a)anthracene 7,12‐dimethylbenz(a)anthracene 9,10-Dimethyl-1,2-benzanthracene Animals Biological and medical sciences breast cancer Cancer chemical carcinogenesis Female Genes Gynecology. Andrology. Obstetrics Interferon-gamma - analysis Interleukin-12 - analysis Interleukin-17 - analysis Interleukin-23 - analysis Mammary gland diseases Mammary Neoplasms, Experimental - blood supply Mammary Neoplasms, Experimental - chemically induced Mammary Neoplasms, Experimental - immunology Mammary Neoplasms, Experimental - pathology Medical research Medical sciences Mice Mice, Inbred C3H Neovascularization, Pathologic - etiology Rodents T-Lymphocytes, Regulatory - immunology toll-like receptor 4 Toll-Like Receptor 4 - physiology Transforming Growth Factor beta - physiology Tumors Breast disease Toll like receptor 4 chemical carcinogenesis Rodentia Breast cancer Cellular immunity Malignant tumor Carcinogenesis Prevention Mammary gland diseases Carcinogen Vertebrata Mammalia Cancerology Mouse Animal 7,12-dimethylbenz(a)anthracene toll-like receptor 4 Cancer
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Summary:	Toll‐like receptors (TLRs) activate signals that are critically involved in the initiation of adaptive immune responses and many tumorigenic chemicals have been associated with activation of those pathways. To determine the role of TLR‐4 (TLR4) in mammary carcinogenesis, we subjected TLR4 deficient and wild type (WT) mice to oral gavage with carcinogenic polyaromatic hydrocarbon 7,12‐dimethylbenz(a)anthracene (DMBA). TLR4 deficient mice developed more tumors relative to the WT mice. T cells of TLR4 deficient mice produced elevated levels of IL‐17 and lower levels of IFN‐γ relative to WT mice. IL‐12 secreted by CD11c+ cells was higher in WT mice, whereas greater amounts of IL‐23 were produced by CD11c+ cells from TLR4 deficient mice. Moreover, there was higher incidence of regulatory T cells in TLR4 deficient mice than WT mice. Similarly, various markers of angiogenesis [matrix metalloproteinases (MMP)‐2 and MMP‐9, CD31 and vascular endothelial growth factor] were highly expressed in tumors from TLR4 deficient mice than WT mice. The results of this study indicate that TLR4 plays an important role in the prevention of DMBA induced mouse mammary tumorigenesis and efforts to divert the cell‐mediated immune response may, therefore, prove to be beneficial in the prevention of mammary tumors.
Bibliography:	ArticleID:IJC26100 ark:/67375/WNG-FMLQX7X9-C Veterans Administration Merit Review Award - No. 18-103-02 istex:0C5B707DEDA8242F6A158371FB9735B548353017 Tel: +205‐934‐7432, Fax: +205‐934‐5745 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0020-7136 1097-0215
DOI:	10.1002/ijc.26100