Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China.
Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China.
Cell Immunol. 2019 Oct;344:103959. doi: 10.1016/j.cellimm.2019.103959. Epub 2019 Jul 29.
Aquaporin (AQP4) could be associated with inflammation, common in central nervous system diseases. We investigated the effect of lipoxin A4 (LXA4) on the activation of astrocytes, AQP4 expression, and inflammatory response induced by lipopolysaccharide (LPS). Astrocytes were cultured in vitro and changes in transcript and protein levels of AQP4, interleukin-1β (IL-1β), tumor necrosis factor-alpha (TNF-α), and cyclooxygenase-2 (COX-2), and protein levels of P38 and phospho-P38 were determined. The LPS group showed increased AQP4, IL-1β, TNF-α, and COX-2 levels, whereas they decreased in the LPS + LXA4 group, suggesting that LXA4 inhibits AQP4 expression. Furthermore, levels of phospho-P38 increased in the LPS group, but decreased in the LPS + LXA4 group. In conclusion, LXA4 alleviated the LPS-induced increase in AQP4 expression and inflammatory cytokine secretion by astrocytes, possibly by inhibiting P38 phosphorylation. For the first time, we found that LXA4 may inhibit the expression of inflammatory factors by regulating the expression of AQP4. AQP4 on astrocytes is likely to be the target of anti-inflammatory effect of LXA4.
水通道蛋白（AQP4）可能与中枢神经系统疾病中的炎症有关。我们研究了脂氧素 A4（LXA4）对脂多糖（LPS）诱导的星形胶质细胞激活、AQP4 表达和炎症反应的影响。体外培养星形胶质细胞，测定 AQP4、白细胞介素-1β（IL-1β）、肿瘤坏死因子-α（TNF-α）和环氧化酶-2（COX-2）的转录和蛋白水平以及 P38 和磷酸化 P38 的蛋白水平的变化。LPS 组 AQP4、IL-1β、TNF-α和 COX-2 水平升高，而 LPS+LXA4 组则降低，表明 LXA4 抑制 AQP4 表达。此外，LPS 组磷酸化 P38 水平升高，而 LPS+LXA4 组则降低。综上所述，LXA4 通过抑制 P38 磷酸化减轻 LPS 诱导的星形胶质细胞 AQP4 表达和炎症细胞因子分泌增加。我们首次发现，LXA4 可能通过调节 AQP4 的表达来抑制炎症因子的表达。星形胶质细胞上的 AQP4 可能是 LXA4 抗炎作用的靶点。
