Eph receptors are involved in the pro-inflammatory response following spinal cord injury (54.21)

Abstract

Abstract Following spinal cord injury (SCI), residential microglia and astrocytes in the spinal cord are known to activate an innate immune response. Here, we examined a role for EphB3 and EphA4 receptors in the early immune response following SCI. Our results demonstrate that EphB3 and EphA4 are present on both microglia and astrocytes in the adult spinal cord, and that they are phosphorylated within 15 min after the initiation of injury. Receptor activation by the ligand ephrinB3 is thought to enhance multiple cytokine mRNA transcripts involved in the immune response, as well as mediate the release of several pro-inflammatory cytokines in vitro. These responses are significantly attenuated in cells derived from mice deficient for EphB3 and EphA4. Interestingly, analysis of the whole spinal cord, using ELISA Assay, showed a significant attenuation in interleukin-6 (IL-6) in astrocytes but not microglia derived from EphB3/EphA4 double knockout (EphB3/A4-/-) mice. To examine cytokine levels following SCI, we collected spinal cord tissues from sham or SCI wild type (WT) and EphB3/A4-/- mice at 4 and 24 hours and analyzed cytokine levels using cytometric bead array. We observed a significant increase in IL-6 and chemokine ligand 2 (CCL-2) at 4 and 24 hours post-SCI in WT but not EphB3/A4-/- mice. These data suggest a novel role for EphB3 and EphA4 in the early activation of the acute immune response, and possibly the progression of damage to the injured spinal cord.