title: Histamine inhibits high mobility group box 1-induced adhesion molecule expression on human monocytes.
abstract: 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 H2-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.
authors.affiliation: Department of Pharmacology, Kinki University, Faculty of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama, Osaka 589-8511, Japan. Electronic address: hkt@med.kindai.ac.jp.
authors.forename: Hideo
authors.initials: H
authors.lastname: Takahashi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sadamori
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Teshigawara
authors.forename: Atsuko
authors.initials: A
authors.lastname: Niwa
authors.forename: Keyue
authors.initials: K
authors.lastname: Liu
authors.forename: Hidenori
authors.initials: H
authors.lastname: Wake
authors.forename: Shuji
authors.initials: S
authors.lastname: Mori
authors.forename: Tadashi
authors.initials: T
authors.lastname: Yoshino
authors.forename: Masahiro
authors.initials: M
authors.lastname: Nishibori
mesh_terms: D049109:Cell Proliferation / Q000187:drug effects; D000242:Cyclic AMP / Q000096:biosynthesis; D005786:Gene Expression Regulation / Q000187:drug effects*; D024243:HMGB1 Protein / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D006632:Histamine / Q000494:pharmacology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects; D008565:Membrane Proteins / Q000378:metabolism*; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism*; D011970:Receptors, Histamine H2 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D024243:HMGB1 Protein; D008565:Membrane Proteins; D011970:Receptors, Histamine H2; D014409:Tumor Necrosis Factor-alpha; D006632:Histamine; D007371:Interferon-gamma; D000242:Cyclic AMP
keywords: Adhesion molecule; Cyclic adenosine monophosphate; H(2) receptor; High mobility group box 1; Histamine; Monocyte