| RRC ID |
18618
|
| 著者 |
Itoh T, Hamada N, Terazawa R, Ito M, Ohno K, Ichihara M, Nozawa Y, Ito M.
|
| タイトル |
Molecular hydrogen inhibits lipopolysaccharide/interferon γ-induced nitric oxide production through modulation of signal transduction in macrophages.
|
| ジャーナル |
Biochem Biophys Res Commun
|
| Abstract |
Molecular hydrogen has been reported to be effective for a variety of disorders and its effects have been ascribed to the reduction of oxidative stress. However, we have recently demonstrated that hydrogen inhibits type I allergy through modulating intracellular signal transduction. In the present study, we examined the hydrogen effects on lipopolysaccharide/interferon γ LPS/IFNγ-induced nitric oxide (NO) production in murine macrophage RAW264 cells. Treatment with hydrogen reduced LPS/IFNγ-induced NO release, which was associated with a diminished induction of inducible isoform of nitric oxide synthase (iNOS). Hydrogen treatment inhibited LPS/IFNγ-induced phosphorylation of apoptosis signal-regulating kinase 1 (ASK1) and its downstream signaling molecules, p38 MAP kinase and JNK, as well as IκBα, but did not affect activation of NADPH oxidase and production of reactive oxygen species (ROS). As ROS is an upstream activator of ASK1, inhibition of ASK1 by hydrogen without suppressing ROS implies that a potential target molecule of hydrogen should be located at the receptor or immediately downstream of it. These results suggested a role for molecular hydrogen as a signal modulator. Finally, oral intake of hydrogen-rich water alleviated anti-type II collagen antibody-induced arthritis in mice, a model for human rheumatoid arthritis. Taken together, our studies indicate that hydrogen inhibits LPS/IFNγ-induced NO production through modulation of signal transduction in macrophages and ameliorates inflammatory arthritis in mice, providing the molecular basis for hydrogen effects on inflammation and a functional interaction between two gaseous signaling molecules, NO and molecular hydrogen.
|
| 巻・号 |
411(1)
|
| ページ |
143-9
|
| 公開日 |
2011-7-22
|
| DOI |
10.1016/j.bbrc.2011.06.116
|
| PII |
S0006-291X(11)01096-5
|
| PMID |
21723254
|
| MeSH |
Animals
Arthritis, Experimental / drug therapy
Cell Line
Female
Hydrogen / administration & dosage
Hydrogen / pharmacology*
Interferon-gamma / immunology
Lipopolysaccharides / immunology
Macrophages / drug effects*
Macrophages / immunology
Mice
Mice, Inbred BALB C
Nitric Oxide / antagonists & inhibitors*
Nitric Oxide / biosynthesis
Nitric Oxide Synthase Type II / antagonists & inhibitors
Nitric Oxide Synthase Type II / biosynthesis
Signal Transduction / drug effects
|
| IF |
2.985
|
| 引用数 |
55
|
|
WOS 分野
|
BIOPHYSICS
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
RAW 264(RCB0535) |
