ARA290, an alternative of erythropoietin, inhibits activation of NLRP3 inflammasome in schwann cells after sciatic nerve injury

Abstract

The challenge of repairing peripheral nerve injury is a critical issue that needs to be addressed urgently. Previous research has shown that erythropoietin (EPO) and its prolonged peptides exhibit beneficial effects in neurological disorders. In our study, we demonstrated that both EPO and pyroglutamic acid helix B surface peptide (pHBSP, also known as ARA290) inhibit the early inflammatory response and promote functional recovery after sciatic nerve crush injury in rat models. Our experimental results demonstrate that significant inflammatory response occurred in Schwann cells after sciatic nerve injury, and that the activation of NLRP3 inflammasome in Schwann cells is inhibited after EPO and ARA290 treatment. Our study further demonstrated that EPO and ARA290 inhibit the activation of NLRP3 inflammasome in Schwann cells by inhibiting NF-κB phosphorylation and reducing reactive oxygen species (ROS) production. In summary, EPO and ARA290 promote repair and regeneration by inhibiting the activation of NLRP3 inflammasome after sciatic nerve injury.