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Papers of the Week

Papers: 9 Nov 2019 - 15 Nov 2019

Animal Studies

2020 May

Cell Mol Neurobiol



Annexin-1 Mimetic Peptide Ac2-26 Suppresses Inflammatory Mediators in LPS-Induced Astrocytes and Ameliorates Pain Hypersensitivity in a Rat Model of Inflammatory Pain.



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.