Article date: July 2018
By: Jidong Guo, Huadong Wang, Li Li, Yanli Yuan, Xiuxiu Shi, Shuxun Hou in Volume 175, Issue 13, pages 2611-2621
Background and Purpose
IL‐19 skews the immune response towards a Th2 type and appears to stimulate angiogenesis. In the current study, we tested if IL‐19 treatment could reduce secondary injury and improve functional recovery after contusion spinal cord injury (SCI).
Experimental Approach
Firstly, mice were given a moderate–severe thoracic SCI at the T9–10 level and expression of IL‐19 and its receptor was measured in the injured spinal cord. Then SCI mice were treated with mouse recombinant IL‐19 and its blocking antibody to investigate the therapeutic effect of IL‐19.
Key Results
Protein expression of IL‐19 and its receptor IL‐20R1 and IL‐20R2 was up‐regulated in the injured spinal cord of mice. IL‐19 treatment promoted the recovery of locomotor function dose‐dependently and reduced loss of motor neurons and microglial and glial activation following SCI. Treatment of SCI mice with IL‐19 attenuated macrophage accumulation, reduced protein levels of TNF‐α and CCL2 and promoted Th2 response and M2 macrophage activation in the injured region. Treatment of SCI mice with IL‐19 promoted angiogenesis through up‐regulating VEGF in the injured region. Treatment of SCI mice with IL‐19 up‐regulated HO‐1 expression and decreased oxidative stress in the injured region. The beneficial effect of IL‐19 was abolished by coadministration of the blocking antibody. Additionally, IL‐19 deficiency in mice delayed the recovery of locomotor function following SCI.
Conclusions and Implications
IL‐19 treatment reduced secondary injuries and improved locomotor functional recovery after contusion SCI, through diverse mechanisms including immune cell polarization, angiogenesis and anti‐oxidative responses.
DOI: 10.1111/bph.14193
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