Juzentaihoto, a Kampo medicine, enhances IL-12 production by modulating Toll-like receptor 4 signaling pathways in murine peritoneal exudate macrophages

Juzentaihoto (TJ-48), a Kampo medicine, has been reported to affect the immune system. Although toll-like receptors (TLRs) have been identified as receptors of innate immunity, the effects of TJ-48 on TLR signaling pathways have not been thoroughly investigated. Here we evaluated the effects of TJ-4...

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Bibliographic Details
Published in:International immunopharmacology 2005-05, Vol.5 (5), p.871-882
Main Authors: Chino, Atsushi, Sakurai, Hiroaki, Choo, Min-Kyung, Koizumi, Keiichi, Shimada, Yutaka, Terasawa, Katsutoshi, Saiki, Ikuo
Format: Article
Language:English
Subjects:
Administration, Oral
Animals
Biological and medical sciences
Drugs, Chinese Herbal - administration & dosage
Drugs, Chinese Herbal - chemistry
Drugs, Chinese Herbal - pharmacology
Female
Immunologic Factors - administration & dosage
Immunologic Factors - chemistry
Immunologic Factors - pharmacology
In Vitro Techniques
Innate immunity
Interleukin-12 - biosynthesis
Interleukin-12 Subunit p40
Juzentaihoto (TJ-48)
Lipopolysaccharides - pharmacology
Macrophages
Macrophages, Peritoneal - drug effects
Macrophages, Peritoneal - immunology
MAP Kinase Signaling System - drug effects
Medical sciences
Mice
Mice, Inbred BALB C
Mitogen-activated protein kinase
Models, Immunological
Molecular Structure
NF-kappa B - antagonists & inhibitors
Nuclear factor κB
Pharmacology. Drug treatments
Protein Subunits - biosynthesis
Receptors, Immunologic - metabolism
Signal Transduction - drug effects
Toll-Like Receptor 4
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Summary:Juzentaihoto (TJ-48), a Kampo medicine, has been reported to affect the immune system. Although toll-like receptors (TLRs) have been identified as receptors of innate immunity, the effects of TJ-48 on TLR signaling pathways have not been thoroughly investigated. Here we evaluated the effects of TJ-48 on TLR4 signaling pathways. Peritoneal exudate macrophages (PEMs) isolated from mice orally administered TJ-48 for 11 days were stimulated with lipopolysaccharide (LPS), a ligand of TLR4, in vitro. Production of IL-12 p40 was significantly augmented in TJ-48-treated PEMs compared with that in vehicle PEMs, without affecting the surface expression of TLR4. Treatment with chemical inhibitors of NF-κB and p38 mitogen-activated protein kinases (MAPKs) in vitro inhibited LPS-induced IL-12 production, whereas JNK and ERK inhibitors increased IL-12 production. Immunoblotting with phosphorylation-state specific antibodies demonstrated that TJ-48 differentially affected LPS-induced phosphorylation of NF-κB and MAPKs. In PEMs treated with TJ-48, LPS-induced phosphorylation of p65 NF-κB and p38 MAPK was augmented, while that of JNK and ERK was attenuated compared with those in vehicle PEMs. These results suggest that selective modulation of the TLR4 signaling pathways by TJ-48 is involved in enhanced production of IL-12 in PEMs.
ISSN:1567-5769
1878-1705
DOI:10.1016/j.intimp.2005.01.004