| First Author | Dai W | Year | 2018 |
| Journal | Int J Mol Med | Volume | 42 |
| Issue | 3 | Pages | 1716-1722 |
| PubMed ID | 29956748 | Mgi Jnum | J:323049 |
| Mgi Id | MGI:6883420 | Doi | 10.3892/ijmm.2018.3749 |
| Citation | Dai W, et al. (2018) AQP4knockout alleviates the lipopolysaccharideinduced inflammatory response in astrocytes via SPHK1/MAPK/AKT signaling. Int J Mol Med 42(3):1716-1722 |
| abstractText | To date, aquaporin4 (AQP4) has been considered as a critical contributor to neuroinflammation, but little is known about the underlying mechanism. Previous studies have shown that a critical enzyme involved in the sphingomyelin cycle, sphingosine kinase 1 (SPHK1), is implicated in inflammatory processes and contributes to chronic neuroinflammation. The present study investigated the role of AQP4 in proinflammatory cytokine release from astrocytes, with an emphasis on the SPHK1/mitogenactivated protein kinase (MAPK)/protein kinase B (AKT) pathway. Using primary cultures isolated from AQP4+/+ and AQP4/ embryos, the production of tumor necrosis factoralpha (TNFalpha)/interleukin6 (IL6) from astrocytes challenged by lipopolysaccharide (LPS) was compared. The results showed increased secretion of TNFalpha/IL6 in the two groups following LPS treatment, but a significantly lower level was observed in the AQP4/ group compared with that in the AQP4+/+ group. Although upregulation of SPHK1 was detected in the two genotypes, only a mild increase in SPHK1 was found in the AQP4/ genotype. The phosphorylation of MAPK/AKT was also confirmed to be attenuated in the AQP4/ group, suggesting decreased MAPK/AKT signaling over time in AQP4/ astrocytes. Overall, the study findings demonstrated that AQP4 deficiency alleviates proinflammatory cytokine release from astrocytes, in association with the SPHK1/MAPK/AKT pathway. This data improves our understanding of AQP4 in neuroinflammatory events, highlighting a novel profile of SPHK1 as a potential target for the treatment of CNS inflammation. |
