| RRC ID |
42391
|
| 著者 |
Mitani T, Terashima M, Yoshimura H, Nariai Y, Tanigawa Y.
|
| タイトル |
TGF-beta1 enhances degradation of IFN-gamma-induced iNOS protein via proteasomes in RAW 264.7 cells.
|
| ジャーナル |
Nitric Oxide
|
| Abstract |
TGF-beta1 is a well-known immunosuppressive cytokine that inhibits inducible nitric oxide synthase (iNOS) gene expression in various cells including macrophages. In this study, we investigated the suppressive mechanisms of TGF-beta1 on IFN-gamma-induced iNOS gene expression using the murine macrophage-like cell line RAW 264.7. TGF-beta1 decreased iNOS protein amount through enhanced degradation, although TGF-beta1 did not affect IFN-gamma-induced iNOS mRNA level or stability. In addition, the enhancement of iNOS protein degradation by TGF-beta1 treatment was almost completely blocked by MG132, a proteasome inhibitor. Furthermore, TGF-beta1 enhanced the trypsin-like activity of proteasomes in the presence of IFN-gamma, although did not enhance the peptidylglutamyl-peptide hydrolyzing and chymotrypsin-like activities of proteasomes. The level of ubiquitinated iNOS protein was not significantly altered by IFN-gamma or IFN-gamma plus TGF-beta1 treatment. Because MG132 inhibited iNOS protein degradation and IFN-gamma plus TGF-beta1 treatment increased the trypsin-like activity of proteasomes, we hypothesized that TGF-beta1 might enhance iNOS protein degradation via the ubiquitin-proteasome pathway in the presence of IFN-gamma. We propose that these mechanisms of TGF-beta1 in the posttranslational regulation of iNOS gene expression may contribute to suppression of excess nitric oxide during inflammatory processes.
|
| 巻・号 |
13(1)
|
| ページ |
78-87
|
| 公開日 |
2005-8-1
|
| DOI |
10.1016/j.niox.2005.05.001
|
| PII |
S1089-8603(05)00066-2
|
| PMID |
15964225
|
| MeSH |
Animals
Cell Line
Dose-Response Relationship, Drug
Gene Expression Regulation, Enzymologic / drug effects*
Interferon-gamma / pharmacology*
Leupeptins / pharmacology
Macrophages / drug effects
Macrophages / metabolism
Mice
Multienzyme Complexes
Nitric Oxide Synthase / metabolism*
Nitric Oxide Synthase Type II
Proteasome Endopeptidase Complex / metabolism*
RNA, Messenger / metabolism
Time Factors
Transcription, Genetic / drug effects
Transforming Growth Factor beta / pharmacology*
Transforming Growth Factor beta1
Ubiquitin / metabolism
|
| IF |
3.311
|
| 引用数 |
38
|
|
WOS 分野
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
CELL BIOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
RAW 264(RCB0535) |
