title: Histamine inhibits lipopolysaccharide-induced tumor necrosis factor-alpha production in an intercellular adhesion molecule-1- and B7.1-dependent manner.
abstract: Lipopolysaccharide (LPS) is recognized as a key molecule in the pathogenesis of Gram negative sepsis and septic shock. In the present study, we demonstrate that LPS (1-1000 pg/ml) concentration dependently up-regulated the expression of intercellular adhesion molecule (ICAM)-1, B7.1, and B7.2 on human monocytes using fluorescence-activated cell sorting analysis, and that tumor necrosis factor (TNF)-alpha production induced by LPS in peripheral blood mononuclear cells (PBMCs) was inhibited by the addition of antibodies against these adhesion molecules, suggesting the dependence of TNF-alpha production on cell-cell interaction through these adhesion molecules. Moreover, we found that histamine (10(-7)-10(-4) M) concentration dependently inhibited the expression of ICAM-1 and B7.1, but not B7.2 on monocytes induced by LPS. Histamine also inhibited the responses of TNF-alpha production induced by LPS. The modulatory effects of histamine on ICAM-1 and B7.1 expression and TNF-alpha production were all concentration dependently antagonized by famotidine but not by d-chlorpheniramine and thioperamide, and were mimicked by selective H2-receptor agonists but not by H1-, H3-, and H4-receptor agonists, indicating the involvement of H2-receptors in the histamine action. Dibutyryl cAMP down-regulated ICAM-1 and B7.1 expression on monocytes stimulated by LPS, suggesting the mediation by the cyclic adenosine monophosphate-protein kinase A pathway of H2-receptor activation. These results as a whole indicated that histamine via H2-receptor inhibited the LPS-induced TNF-alpha production through the regulation of ICAM-1 and B7.1 expression, leading to the reduction of innate immune response stimulated by LPS.
authors.affiliation: Department of Tumour Biology, Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Morichika
authors.forename: Hideo Kohka
authors.initials: HK
authors.lastname: Takahashi
authors.forename: Hiromi
authors.initials: H
authors.lastname: Iwagaki
authors.forename: Tadashi
authors.initials: T
authors.lastname: Yoshino
authors.forename: Ryuji
authors.initials: R
authors.lastname: Tamura
authors.forename: Minori
authors.initials: M
authors.lastname: Yokoyama
authors.forename: Shuji
authors.initials: S
authors.lastname: Mori
authors.forename: Tadaatsu
authors.initials: T
authors.lastname: Akagi
authors.forename: Masahiro
authors.initials: M
authors.lastname: Nishibori
authors.forename: Noriaki
authors.initials: N
authors.lastname: Tanaka
mesh_terms: D018122:B7-1 Antigen / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D006632:Histamine / Q000494:pharmacology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis*; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*
chemical_list: D018122:B7-1 Antigen; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D006632:Histamine