Role of MK2 signaling pathway mediating microglia/macrophages polarization in chronic compression injury of cervical spinal cord.

Abstract

The role of inflammatory factors in the chronic compression injury of cervical spinal cord has drawn more attenion recently, however, the mechanism of which is still unclear. In this study, microglia/ macrophages polarization in the inflammatory responses to the injury and its regulation by MK2 signaling pathway have been investigated. twy/twy mice at the age of 6-24 weeks were used in the animal model for the chronic compression of cervical spinal cord. ICR (Institute of Cancer Research) mice were used as the control group. MK2 inhibitor (PF-3644022, 30 mg/kg) was administrated intragastrically to twy/twy mice from weeks 20 to 24. The compression of cervical spinal cord was identified by CT/MRI. The cervical spinal cord between C2 and C3 of vertebral segments were investigated by Western blot and Real-time PCR. The animal behaviors were evaluated by BMS score. Western blot and Real-time PCR showed that the expressions of iNOS and Arg-1 in the compressed spinal cord of twy/twy mice were significantly higher than those of the control group. After treatment with PF-3644022, the expression of Arg1 was increased while that of iNOS decreased. Realtime PCR revealed the increased expressions of inflammation related factors (such as IL-1β, NF-κB, TNF-α, MK2) and pro-apoptotic gene (Bax) except the decreased expression of anti-apoptotic gene (Bcl-2). Nevertheless, such increases were vanished after treatment of PF-3644022 except an increased expression of Bcl-2. The BMS score showed a reduced motor function of the twy/twy mice. The motor function was enhanced again with the treatment of PF-3644022. Microglia/macrophages polarization may be involved in the inflammatory response to the chronic compression of cervical spinal cord. It can be regulated by the MK2 signaling pathway. Therefore, it is possible to relieve the chronic compression of cervical spinal cord by regulating microglia/macrophages polarization through MK2 signaling pathway.