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
| Autor: | Takahiro A. Kato, Hidetoshi Tozaki-Saitoh, Masako Hosoi, Makoto Tsuda, Tomohiro Yamashita, Izumi Sasaki |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Agonist Adrenergic receptor medicine.drug_class Interleukin-1beta Gene Expression Proinflammatory cytokine Mice Norepinephrine 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation Proto-Oncogene Proteins Receptors Adrenergic beta medicine Animals Receptor Intracellular signaling cascade Cells Cultured Neuroinflammation Pharmacology Inflammation Reporter gene Microglia Chemistry lcsh:RM1-950 Isoproterenol Adrenergic beta-Agonists MAP Kinase Kinase Kinases Acetylcysteine Erythromycin Up-Regulation Cell biology 030104 developmental biology medicine.anatomical_structure lcsh:Therapeutics. Pharmacology Molecular Medicine 030217 neurology & neurosurgery Signal Transduction |
| Zdroj: | Journal of Pharmacological Sciences, Vol 143, Iss 3, Pp 133-140 (2020) |
| ISSN: | 1347-8613 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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