| First Author | Ke P | Year | 2017 |
| Journal | CNS Neurosci Ther | Volume | 23 |
| Issue | 11 | Pages | 875-884 |
| PubMed ID | 28941191 | Mgi Jnum | J:328397 |
| Mgi Id | MGI:6880907 | Doi | 10.1111/cns.12758 |
| Citation | Ke P, et al. (2017) Activating alpha7 nicotinic acetylcholine receptor inhibits NLRP3 inflammasome through regulation of beta-arrestin-1. CNS Neurosci Ther 23(11):875-884 |
| abstractText | AIMS: To evaluate whether activating alpha7 nicotinic acetylcholine receptor (alpha7nAChR) could inhibit the NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome through regulation of beta-arrestin-1 in monocyte/macrophage system, thus contributing to the control of neuroinflammation. METHODS: The protein levels of NLRP3, caspase-1 (Casp-1) p20 and proCasp-1, interleukin-1beta (IL-1beta) p17 and proIL-1beta, IL-18 and proIL-18 were measured using Western blotting. The mRNA levels of Casp-1 and IL-1beta were detected by real-time PCR (RT-PCR). The colocalization and interaction of NLRP3 protein and beta-arrestin-1 were measured by immunofluorescence staining and immunoprecipitation. RESULTS: The expression of beta-arrestin-1 was significantly increased and colocalized with CD45-positive cells in spinal cord of experimental auto-immune encephalomyelitis (EAE) mice when compared with the sham mice, which was attenuated by pretreatment with PNU282987, a specific alpha7nAChR agonist. PNU282987 also significantly inhibited the activation of NLRP3 inflammasome and thus decreased the production of IL-1beta and IL-18 both in lipopolysaccharide (LPS)/ATP-stimulated BV2 microglia in vitro and spinal cord from EAE mice in vivo, while inverse effects were observed in alpha7nAChR knockout mice. Furthermore, overexpression of beta-arrestin-1 attenuated the inhibitory effect of PNU282987 on NLRP3 inflammasome activation in LPS/ATP-stimulated BV2 microglia. PNU282987 inhibited the interaction between beta-arrestin-1 and NLRP3 protein in vitro. CONCLUSIONS: The present study demonstrates that activating alpha7nAChR can lead to NLRP3 inflammasome inhibition via regulation of beta-arrestin-1 in monocyte/microglia system. |
