2004 Fiscal Year Final Research Report Summary
Regulatory mechanisms of uncoupling protein 2 (an anti-obesity molecule) expression: the application to preventive medicine
| Project/Area Number |
15590521
|
|---|
| 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, 医学部, 助教授 (00322446)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
OHNO Hideki Kyorin University, School of Medicine, Professor, 医学部, 教授 (00133819)
|
|---|
| Project Period (FY) |
2003 – 2004
|
| Keywords | macrophage / uncoupling protein 2 / β2-adrenergic receptor / exercise training / LPS / IL-12 / Th 1 / Th 2 |
|---|
| Research Abstract |
Three-week exercise training decreased the steady state level of β_2-adrenergic receptor (β_2AR) mRNA in peritoneal macrophages from BALB/c mice. When peritoneal macrophages from both exercise-trained and sedentary control mice were stimulated with lipopolysaccharide (LPS), interleukin (IL)-12 mRNA and protein expression was markedly higher in trained mice than in control mice. To determine whether enhanced production of IL-12 was associated with decreased expression of β_2AR, we transfected the macrophage cell line, RAW264, with an eukaryotic expression vector containing β_2ar cDNA, establishing a cell line overexpressing β_2AR (RAWar). Following LPS stimulation, IL-12 mRNA and protein expression was significantly lower in RAWar cells than in RAW264 cells transfected with vector alone (RAWvec). Furthermore, when the expression of transfected β_2AR in RAWar cells was down-regulated by a tetracycline repressor-regulated mammalian expression system, expression of IL-12 mRNA and protein following LPS stimulation tended to return to the levels in RAWvec cells. These findings indicate that macrophage production of IL-12 following LPS stimulation is regulated by the expression level of β_2AR, suggesting that the down-regulation of β_2AR expression associated with exercise training improves IL-12-induced type 1 helper T (Th 1) cell-mediated immune responses.
The expression of uncoupling protein 1 (UCP 1), a member of the UCP family, is known to be regulated by β_3AR in adipose tissues. We previously demonstrated that UCP2 expression is regulated by LPS stimulation in macrophages. UCP2 and β_2AR are dominantly expressed in macrophages, suggesting the cross-talk between the regulatory system of UCP 2 expression by β_2AR and the LPS induced signal transduction cascade.
|
