Ac2-26, a mimetic peptide of Annexin-A1, plays a vital role in the anti-inflammatory response mediated by astrocytes. In this study, we aimed to explore the underlying mechanisms of Ac2-26-mediated anti-inflammatory effect. Specifically, we investigated the inhibitory effects of Ac2-26 on lipopolysaccharide (LPS)-induced astrocyte migration and on pro-inflammatory cytokines and chemokines expressions, as well as one glutathione (GSH) reductase mRNA and total intracellular GSH levels in LPS-induced astrocytes. Additionally, we investigated whether mitogen-activated protein kinases (MAPK) and nuclear factor kappa-B (NF-κB) signaling pathway were involved in this process. Finally, we evaluated the analgesic effect of Ac2-26 in complete Freund's adjuvant (CFA)-induced inflammatory pain model. Our results demonstrated that Ac2-26 inhibited LPS-induced astrocytes migration, reduced the production of pro-inflammatory mediators [tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1 (MIP-1α)] and upregulated GSH reductase mRNA and GSH levels in LPS-induced astrocytes in vitro. This process was mediated through the p38, JNK-MAPK signaling pathway, but not dependent on the NF-κB pathway. Furthermore, the p38 and JNK inhibitors mimicked the effects of Ac2-26, whereas a p38 and JNK activator anisomycin partially reversed its function. Finally, Ac2-26 treatment reduced CFA-induced activation of astrocytes and production of inflammatory mediators in the spinal cord. These results suggest that Ac2-26 attenuates pain by inhibiting astrocyte activation and the production of inflammatory mediators; thus, this work presents Ac2-26 as a potential drug to treat neuropathic pain.

中文翻译：

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Annexin-1模拟肽Ac2-26抑制LPS诱导的星形胶质细胞中的炎症介质，并减轻了大鼠炎性疼痛的疼痛超敏性。

Ac2-26是膜联蛋白A1的模拟肽，在星形胶质细胞介导的抗炎反应中起着至关重要的作用。在这项研究中，我们旨在探讨Ac2-26介导的抗炎作用的潜在机制。具体来说，我们研究了Ac2-26对脂多糖（LPS）诱导的星形胶质细胞迁移以及促炎性细胞因子和趋化因子表达以及LPS诱导的星形胶质细胞中一种谷胱甘肽（GSH）还原酶mRNA和总细胞内GSH水平的抑制作用。 。此外，我们调查了有丝分裂原激活的蛋白激酶（MAPK）和核因子kappa-B（NF-κB）信号通路是否参与此过程。最后，我们评估了Ac2-26在完全弗氏佐剂（CFA）诱导的炎性疼痛模型中的镇痛作用。我们的结果表明，Ac2-26抑制LPS诱导的星形胶质细胞迁移，减少促炎性介质的产生[肿瘤坏死因子-α（TNF-α），白介素-1β（IL-1β），单核细胞趋化蛋白1（MCP -1）和巨噬细胞炎性蛋白1（MIP-1α）]，并在LPS诱导的星形胶质细胞中上调GSH还原酶mRNA和GSH水平。该过程通过p38，JNK-MAPK信号传导途径介导，但不依赖于NF-κB途径。此外，p38和JNK抑制剂模仿了Ac2-26的作用，而p38和JNK激活剂茴香霉素则部分逆转了其功能。最后，Ac2-26处理减少了CFA诱导的星形胶质细胞活化和脊髓炎性介质的产生。这些结果表明，Ac2-26通过抑制星形胶质细胞的活化和炎性介质的产生来减轻疼痛。因此，这项工作提出Ac2-26作为治疗神经性疼痛的潜在药物。