T1R1/T1R3 Taste Receptor Suppresses Granulocyte-Mediated Neuroinflammation after Spinal Cord Injury

As an active and predominant blood leukocyte population, granulocytes infiltrate into injured spinal cord and produce pro-inflammatory mediators to aggravate neuroinflammation. In the current study, we identify the role of the T1R1/T1R3 receptor in granulocyte-mediated neuroinflammation in a rat spinal cord injury (SCI) model. We found that T1R1 and T1R3 were substantially expressed in both circulating and infiltrating granulocytes. In vitro stimulation of T1R1/T1R3 receptor with L-serine notably reduced production of reactive oxygen species (ROS) and several pro-inflammatory cytokines. To evaluate the role of T1R1/T1R3 receptor in vivo, gurmarin, a selective T1R3 inhibitor, was injected into rats before and after SCI. Gurmarin administration significantly upregulated expression of interleukin (IL)-1 beta, IL-6, myeloperoxidase, and matrix metallopeptidase 9, as well as production of ROS in infiltrating granulocytes. Signal pathway analysis revealed that gurmarin promoted nuclear factor (NF)-kappa beta signaling in infiltrating granulocytes. Consistently, cell apoptosis and inflammatory mediator levels at the injury sites were increased by gurmarin, together with higher T lymphocyte recruitment. Our research indicates that the T1R1/T1R3 receptor is an anti-inflammatory receptor for infiltrating granulocytes after SCI. Simulation of T1R1/T1R3 receptor might be a prospective, or at least a supplemental, therapeutic approach to controlling neuroinflammation to promote functional recovery.