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.
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 4-6 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 - 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.
Funayama
Hiromi
H
Department of Microbiology and Immunology, Tohoku University School of Dentistry, Sendai, Japan.
Huang
Ling
L
Asada
Yoshinobu
Y
Endo
Yasuo
Y
Takada
Haruhiko
H
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000494:pharmacology; D000818:Animals; D003960:Diaminopimelic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D006632:Histamine / Q000378:metabolism; D006640:Histidine Decarboxylase / Q000096:biosynthesis*; D007202:Indicators and Reagents; D008050:Lipid A / Q000494:pharmacology; D008168:Lung / Q000187:drug effects / Q000201:enzymology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D053474:Nod1 Signaling Adaptor Protein / Q000494:pharmacology*; D053473:Nod2 Signaling Adaptor Protein / Q000494:pharmacology*; D009842:Oligopeptides / Q000494:pharmacology; D051193:Toll-Like Receptors / Q000819:agonists*
D007202:Indicators and Reagents; D008050:Lipid A; D053474:Nod1 Signaling Adaptor Protein; D053473:Nod2 Signaling Adaptor Protein; D009842:Oligopeptides; D051193:Toll-Like Receptors; D000119:Acetylmuramyl-Alanyl-Isoglutamine; D003960:Diaminopimelic Acid; C034330:FK 156; D006632:Histamine; D006640:Histidine Decarboxylase; C039537:heptanoyl-gamma-D-glutamyl-L-meso-diaminopimelyl-D-alanine