| RRC ID |
81464
|
| 著者 |
Tozaki-Saitoh H, Sasaki I, Yamashita T, Hosoi M, Kato TA, Tsuda M.
|
| タイトル |
Involvement of exchange protein directly activated by cAMP and tumor progression locus 2 in IL-1β production in microglial cells following activation of β-adrenergic receptors.
|
| ジャーナル |
J Pharmacol Sci
|
| Abstract |
Endogenous noradrenaline (NA) has multiple bioactive functions and, in the central nervous system (CNS), has been implicated in modulating neuroinflammation via β-adrenergic receptors (β-ARs). Microglia, resident macrophages in the CNS, have a central role in the brain immune system and have been reported to be activated by NA. However, intracellular signaling mechanisms of the AR-mediated proinflammatory responses of microglia are not fully understood. Using a rapid and stable in vitro reporter assay system to evaluate IL-1β production in microglial BV2 cells, we found that NA and the β-AR agonist isoproterenol upregulated the IL-1β reporter activity. This effect was suppressed by β-AR antagonists. We further examined the involvement of EPAC (exchange protein directly activated by cAMP) and TPL2 (tumor progression locus 2, MAP3K8) and found that inhibitors for EPAC and TPL2 reduced AR agonist-induced IL-1β reporter activity. These inhibitors also suppressed NA-induced endogenous Il1b mRNA expression and IL-1β protein production. Our results suggest that EPAC and TPL2 are involved in β-AR-mediated IL-1β production in microglial cells, and extend our understanding of its intracellular signaling mechanism.
|
| 巻・号 |
143(3)
|
| ページ |
133-140
|
| 公開日 |
2020-7-1
|
| DOI |
10.1016/j.jphs.2020.03.004
|
| PII |
S1347-8613(20)30031-1
|
| PMID |
32253104
|
| MeSH |
Acetylcysteine / analogs & derivatives*
Acetylcysteine / pharmacology
Adrenergic beta-Agonists / pharmacology
Animals
Cells, Cultured
Erythromycin / analogs & derivatives*
Erythromycin / pharmacology
Gene Expression / drug effects
Interleukin-1beta / genetics
Interleukin-1beta / metabolism*
Isoproterenol / pharmacology
MAP Kinase Kinase Kinases / pharmacology*
MAP Kinase Kinase Kinases / physiology
Mice
Microglia / metabolism*
Norepinephrine / pharmacology
Norepinephrine / physiology
Proto-Oncogene Proteins / pharmacology*
Proto-Oncogene Proteins / physiology
Receptors, Adrenergic, beta
Signal Transduction
Up-Regulation / drug effects
|
| IF |
2.835
|
| リソース情報 |
| 遺伝子材料 |
pCAG-HIVgp (RDB04394)
pCMV-VSV-G-RSV-Rev (REB04393) |
