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Inducible histamine protects mice from P. acnes-primed and LPS-induced hepatitis through H2-receptor stimulation.

AbstractBACKGROUND & AIMS:
Inducible histamine and histamine H2-receptors have been suggested to be involved in innate immune response.
METHODS:
We examined a functional role of inducible histamine in the protection against hepatic injury and lethality in Propionibacterium acnes -primed and lipopolysaccharide-induced hepatitis, using histidine decarboxylase knockout and H2-receptor knockout mice.
RESULTS:
Lipopolysaccharide challenge after Propionibacterium acnes priming increased histidine decarboxylase activity in the liver of wild-type mice, associated with a marked elevation of histamine turnover. Histidine decarboxylase-like immunoreactivity was observed in CD68-positive Kupffer cells/macrophages. Treatment of wild-type mice with famotidine or ranitidine but not d -chlorpheniramine augmented hepatic injury and inhibited the survival rate significantly. The same dose of Propionibacterium acnes and lipopolysaccharide induced severe hepatitis and high lethality in histidine decarboxylase knockout and H2-receptor knockout mice; the former were rescued by the subcutaneous injection of histamine. Immunohistochemical study supported the protective role of histamine against the apoptosis of hepatocytes. Histamine suppressed the expression of IL-18 and tumor necrosis factor alpha in the liver, leading to the reduced plasma levels of cytokines including IL-18, TNF-alpha, IL-12, IFN-gamma, and IL-6.
CONCLUSIONS:
These findings as a whole indicated that endogenously produced histamine in Kupffer cells/macrophages plays a very important role in preventing excessive innate immune response in endotoxin-induced fulminant hepatitis through the stimulation of H2-receptors.
AuthorsMinori Yokoyama, Akira Yokoyama, Shuji Mori, Hideo K Takahashi, Tadashi Yoshino, Takeshi Watanabe, Takehiko Watanabe, Hiroshi Ohtsu, Masahiro Nishibori
JournalGastroenterology (Gastroenterology) Vol. 127 Issue 3 Pg. 892-902 (Sep 2004) ISSN: 0016-5085 [Print] United States
PMID15362044 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Interleukin-18
  • Lipopolysaccharides
  • Receptors, Histamine H2
  • Tumor Necrosis Factor-alpha
  • Histamine
  • Interferon-gamma
  • Histidine Decarboxylase
Topics
  • Animals
  • Female
  • Gram-Positive Bacterial Infections (complications, immunology)
  • Hepatitis (immunology)
  • Histamine (immunology)
  • Histidine Decarboxylase (immunology)
  • Interferon-gamma (immunology)
  • Interleukin-18 (immunology)
  • Lipopolysaccharides (adverse effects)
  • Liver Failure (immunology, microbiology)
  • Male
  • Mice
  • Mice, Knockout
  • Models, Animal
  • Propionibacterium acnes
  • Receptors, Histamine H2 (immunology)
  • Survival Analysis
  • Tumor Necrosis Factor-alpha (immunology)

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