Abstract
The purpose of the present study was to investigate the influence of lack of histamine (HA) on tumor growth and functions of T cells in order further to illustrate the mechanism of immunological tolerance induction by HA. We assessed the phenotype and cytokine production of splenic lymphocytes in syngeneic HA-free (histidine decarboxylase knock-out) (HDC KO) and wild-type mice, inoculated subcutaneously with the LM2 murine breast cancer cell line. Relative quantification of target mRNA was performed with a TaqMan real-time RT-PCR assay. The CD4(+)CD25(high+) Treg cell numbers were significantly smaller in the tumor-bearing KO mice than in the wild type ones measured by flow-cytometry. The expression of forkhead box P3 (Foxp3) decreased significantly and the copies of splenic Tbox-21 (T-bet) transcriptional factor mRNA was higher in HDC KO tumor-bearing mice than those of normal mice. The cytokine levels showed that a smaller number of interleukin-13-producing Th2 cells were elicited compared to interferon-gamma-producing Th1 cells in the tumor-bearing HDC KO mice. In conclusion, the present study demonstrates that endogenous histamine stimulates the growth of breast adenocarcinoma tumor implants in mice by suppressing anti-tumor immunity.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenocarcinoma / metabolism
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Adenocarcinoma / pathology
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Adenocarcinoma / physiopathology*
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Animals
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CD3 Complex / immunology
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Cell Communication / physiology*
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Cell Differentiation / immunology
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Cell Line, Tumor
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Cytokines / genetics
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Cytokines / metabolism
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Enzyme-Linked Immunosorbent Assay
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Flow Cytometry
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Forkhead Transcription Factors / genetics
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Forkhead Transcription Factors / metabolism
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Histamine / deficiency*
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Histidine Decarboxylase / genetics
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Histidine Decarboxylase / metabolism
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Immunophenotyping
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Interleukin-2 Receptor alpha Subunit / immunology
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Mammary Neoplasms, Experimental / metabolism
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Mammary Neoplasms, Experimental / pathology
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Mammary Neoplasms, Experimental / physiopathology*
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Mice
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Mice, Inbred BALB C
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Mice, Knockout
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Reverse Transcriptase Polymerase Chain Reaction
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Spleen / cytology
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Spleen / immunology
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T-Box Domain Proteins / genetics
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T-Box Domain Proteins / metabolism
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T-Lymphocyte Subsets / immunology
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T-Lymphocyte Subsets / metabolism
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T-Lymphocyte Subsets / physiology
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T-Lymphocytes, Regulatory / immunology
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T-Lymphocytes, Regulatory / metabolism
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T-Lymphocytes, Regulatory / physiology*
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T-bet Transcription Factor
Substances
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CD3 Complex
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Cytokines
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Forkhead Transcription Factors
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Foxp3 protein, mouse
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Interleukin-2 Receptor alpha Subunit
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RNA, Messenger
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T-Box Domain Proteins
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T-bet Transcription Factor
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Histamine
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Histidine Decarboxylase