Histamine inhibits high mobility group box 1-induced adhesion molecule expression on human monocytes

Hideo Takahashi, Hiroshi Sadamori, Kiyoshi Teshigawara, Atsuko Niwa, Keyue Liu, Hidenori Wake, Shuji Mori, Tadashi Yoshino, Masahiro Nishibori

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)


Cell-cell interaction through binding of adhesion molecules on monocytes to their ligands on T-cells plays roles in cytokine production and lymphocyte proliferation. High mobility group box 1 (HMGB1), an abundant and conserved nuclear protein, acts in the extracellular environment as a primary pro-inflammatory signal. HMGB1 induces expression of intercellular adhesion molecule (ICAM), B7.1, B7.2 and CD40 on monocytes, resulting in production of interferon (IFN)-γ and tumor necrosis factor (TNF)-α production and lymphocyte proliferation in human peripheral blood mononuclear cells (PBMCs). Histamine inhibits pro-inflammatory cytokine production via histamine H 2-receptors; however, it is not known whether histamine inhibits HMGB1 activity. This study was designed to study the inhibitory effect of histamine on HMGB1 activity. We examined the effect of histamine on HMGB1-induced expression of ICAM-1, B7.1, B7.2 and CD40 on monocytes, production of IFN-γ and TNF-α and lymphocyte proliferation in PBMCs. Histamine inhibited HMGB1 activity in a concentration-dependent manner. The effects of histamine were partially ablated by the H2-receptor antagonist, famotidine, and mimicked by the H2/H4-receptor agonists, dimaprit and 4-methylhistamine. Histamine induced cyclic adenosine monophosphate (cAMP) production in the presence and absence of HMGB1. The effects of histamine were reversed by the protein kinase A (PKA) inhibitor, H89, and mimicked by the membrane-permeable cAMP analog, dibutyryl cAMP (dbcAMP), and the adenylate cyclase activator, forskolin. These results together indicated that histamine inhibited HMGB1 activity

Original languageEnglish
Pages (from-to)305-313
Number of pages9
JournalEuropean Journal of Pharmacology
Issue number1-3
Publication statusPublished - 2013


  • Adhesion molecule
  • Cyclic adenosine monophosphate
  • H receptor
  • High mobility group box 1
  • Histamine
  • Monocyte

ASJC Scopus subject areas

  • Pharmacology


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