2007 Fiscal Year Final Research Report Summary
Immunomodulation by adrenergic receptor : the application to stress related disease
| Project/Area Number |
18590571
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Hygiene
|
|---|
| Research Institution | Kyorin University |
|---|
Principal Investigator |
KIZAKI Takako Kyorin University, School of Medicine, Associate Professor (00322446)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
OHNO Hideki Kyorin University, School of Medicine, Professor (00133819)
|
|---|
| Project Period (FY) |
2006 – 2007
|
| Keywords | gene / signal transduction / stress / regulation of gene expression / immunology |
|---|
| Research Abstract |
Toll-like receptors (TLRs) play an important role in innate immunity. Meanwhile, β2-adrenergic receptors (b_2AR) provide the key linkages for the sympathetic nervous system to regulate the immune system; however, its role in macrophages remains uncertain. Here, we demonstrated the cross-talk between β_2AR and TLR signaling pathways. β_2AR expression was down-regulated by TLR4 ligand lipopolysaccharide (LPS) stimulation. To investigate the physiological consequence of the down-regulation, the macrohage cell line, RAW264 cells were transfected with β_2AR expression vector (RAWar). LPS-stimulated inducible nitric oxide synthase (NOS II) expression and NO production were markedly suppressed in RAWar cells. The activation of nuclear factor κB (NF-κ13) and degradation of the inhibitor of NF-κB (IκBα) in response to LPS were markedly decreased in these cells. The level of β-arrestin 2, which regulates β_2AR signaling, was also reduced in RAW264 cells after stimulation with LPS, but not in RAW
… More
ar cells. Further, we demonstrated that β-arrestin 2 interacted with cytosolic IκBα and that the level of IκBα co-immunoprecipitated by anti-β-arrestin 2 antibodies was decreased in RAW264 cells but not in RAWar or RAWarr2 cells. These findings suggest that LPS-stimulated signals suppress β_2AR expression, leading to down-regulation of β-arrestin 2 expression, which stabilizes cytosolic IκBα and inhibits the NF-KB activation essential for NOS II expression.
Next, the effects of three-week exercise training on the functions of peritoneal macrophages from BALB/c mice were investigated. LPS-stimulated NO and proinflammatory cytokine production in macrophages from trained mice was markedly higher than those from control mice. Meanwhile, exercise training decreased the steady state level of β_2AR mRNA in macrophages. When expression of transfected β_2AR in RAWar cells was downregulated by a tetracycline repressor-regulated mammalian expression system, NOS II mRNA expression was significantly increased ; this suggested that the changes in the β_2AR expression level in macrophages associated with exercise training play a role in the regulation of NO production following LPS stimulation. These findings indicate that exercise training improves macrophage innate immune function in a β_2AR-dependent and -independent manner. Less
|
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
[Presentation] Antioxidative/ anti-inflammatory effects of the new lychee-derived polyphenol Oligonol converted into a low-molecular form in white adipose tissue2007
Author(s)
Sakurai, T., Nishioka, H., Fujii, H., Kizaki, T., Izawa, T., Shirato, K., Imaizumi, K., Ikeda, S., Haga, S., Ohno, H
Organizer
3rd International Conference on Polyphenols and Health
Place of Presentation
Kyoto
Year and Date
20071125-28
Description
「研究成果報告書概要(欧文)」より
-
-
[Presentation] New lychee-derived polyphenol Oligonol converted into a low-molecular form reduces oxidant stress in adipocytes2007
Author(s)
Sakurai, T., Nishioka, H., Fujii, H., Nakano, N., Kizaki, T., Izawa, T., Haga, S., Ishida, H., Radak, Z., Ohno, H
Organizer
15th European Congresson Obesity
Place of Presentation
Budapest
Year and Date
20070422-25
Description
「研究成果報告書概要(欧文)」より
-
-
-
-
-
[Presentation] β_2-Adrenergic receptor plays a regulatory role in the expression of inducible nitric oxide synthase through β arrestin-2 in macrophages after lipopolysaccharide stimulation2006
Author(s)
Kizaki, T., Nakano, N., Sakurai, T., Ishibashi, Y., Wako, N., Izawa, T., Saitoh, D., Takemasa, T., Haga, S., Ohno, H
Organizer
20th IUBMB International Congress of Biochemistry and Molecular Biology and 11th FAOBMB Congress
Place of Presentation
Kyoto
Year and Date
20060618-23
Description
「研究成果報告書概要(欧文)」より
-
-
[Presentation] The new lychee-derived polyphenol Oligonol converted into a low-molecular form has antioxidative/anti-inflammatory effects in adipocytes
Author(s)
Sakurai, T., Nishioka, H., Fujii, H., Kizaki, T., Shirato, K., Imaizumi, K., Saitoh, D., Ohno, H
Organizer
15th International Symposium of AHCC Research Association
Place of Presentation
Sapporo
Year and Date
00000721-22
Description
「研究成果報告書概要(欧文)」より
-
[Book] 体力とはなにか2007
Author(s)
大野 秀樹, 他
Total Pages
1
Publisher
ナップ
Description
「研究成果報告書概要(和文)」より
-
[Book] 体力とはなにか2007
Author(s)
木崎 節子, 他
Total Pages
5
Publisher
ナップ
Description
「研究成果報告書概要(和文)」より
