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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

^* To whom correspondence should be addressed. E-mail: dent-ht{at}m.tains.tohoku.ac.jp.

	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 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.

First published on August 26, 2009
Innate Immunity 2009, doi:10.1177/1753425909341070


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