Enhanced induction of a histamine-forming enzyme, histidine decarboxylase, in mice primed with NOD1 or NOD2 ligand in response to various Toll-like receptor agonists

Hiromi Funayama, Ling Huang, Yoshinobu Asada, Yasuo Endo, Haruhiko Takada

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)

Abstract

We investigated the immunopharmacological aspects of innate immune responses via Toll-like receptors (TLRs), NOD1 and NOD2, in terms of induction of the histamine-forming enzyme, histidine decarboxylase (HDC), activity in mice. Intravenous injection of TLR4-agonistic synthetic lipid A definitely induced HDC activity in the liver, spleen, and lungs, especially the lungs, in mice, where maximum activity was induced about 3 h after the injection of lipid A. The TLR2/6 agonistic synthetic diacyl-type lipopeptide FSL-1 and TLR3-agonistic poly I:C were also effective in inducing HDC, while the NOD2-agonistic synthetic muramyldipeptide (MDP) and NOD1-agonistic synthetic FK156 and FK565 exhibited only weak activities in this respect. Mice primed with intravenous injection of NOD1 or NOD2 agonists produced higher HDC activity following the 4ĝ€"6 h later intravenous challenge with the above TLR agonists. Among the priming agents, FK565 exhibited the strongest activity, and it was effective via various administration routes ĝ€" intraperitoneal, subcutaneous, intramuscular, as well as intravenous injection; furthermore, oral (gastric) administration was effective, although it needed a dose 10 times higher than that required for other administration routes. These findings suggest that HDC is induced in association with TLRs and NOD1/2, and that the newly formed histamine by the induced HDC might play important roles in the regulation of inflammatory and immune responses in various organs.

Original languageEnglish
Pages (from-to)265-272
Number of pages8
JournalInnate Immunity
Volume16
Issue number4
DOIs
Publication statusPublished - 2010 Aug 1

Keywords

  • NOD1
  • NOD2
  • Toll-like receptors
  • histamine
  • lipid A

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Molecular Biology
  • Cell Biology
  • Infectious Diseases

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