Histamine inhibits lipopolysaccharide-induced tumor necrosis factor-α production in an intercellular adhesion molecule-1- and B7.1-dependent manner

Toshihiko Morichika, Hideo Kohka Takahashi, Hiromi Iwagaki, Tadashi Yoshino, Ryuji Tamura, Minori Yokoyama, Shuji Mori, Tadaatsu Akagi, Masahiro Nishibori, Noriaki Tanaka

Research output: Contribution to journalArticle

43 Citations (Scopus)

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)-α 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-α 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-α production induced by LPS. The modulatory effects of histamine on ICAM-1 and B7.1 expression and TNF-α 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-α production through the regulation of ICAM-1 and B7.1 expression, leading to the reduction of innate immune response stimulated by LPS.

Original languageEnglish
Pages (from-to)624-633
Number of pages10
JournalJournal of Pharmacology and Experimental Therapeutics
Volume304
Issue number2
DOIs
Publication statusPublished - Feb 1 2003

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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