Histamine H2 receptor-mediated modulation of local cytokine expression in a mouse experimental tumor model

Kohji Takahashi, Satoshi Tanaka, Kazuyuki Furuta, Atsushi Ichikawa

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22 Citations (Scopus)

Abstract

Accumulating evidence indicates that histamine is involved in the modulation of cytokine expression patterns. We previously reported that daily treatment with the H2 receptor antagonist, cimetidine, suppressed tumor growth through alteration of the local cytokine expression pattern. In this study, we used a mouse strain genetically lacking histidine decarboxylase (HDC), to evaluate the role of endogenous histamine synthesis on cytokine expression and tumor development. In the mutant mice, cimetidine had no effect on tumor growth, whereas an H2 agonist, dimaprit, significantly enhanced tumor growth. When the HDC-deficient mice were implanted with mutant CT-26 cells stably expressing HDC, drastic suppression of tumor growth by cimetidine was observed, which was accompanied by augmentation of mRNA expression of LT-β, TNF-α, and IFN-γ in the tumor tissues. These results suggest that endogenous histamine synthesis in tumor tissues suppresses local tumor immunity via the H2 receptors, resulting in tumor growth promotion.

Original languageEnglish
Pages (from-to)1205-1210
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume297
Issue number5
DOIs
Publication statusPublished - Nov 6 2002

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Keywords

  • Cimetidine
  • Cytokine
  • Histamine
  • Histamine H receptor
  • Histidine decarboxylase
  • Tumor immunity

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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