The Role of IL-17 Promotes Spinal Cord Neuroinflammation via Activation of the Transcription Factor STAT3 after Spinal Cord Injury in the Rat

Abstract

Study Design. In this study, we investigated the role of IL-17 via activation of STAT3 in the pathophysiology of SCI. Objective. The purpose of the experiments is to study the expression of IL-17 and related cytokines via STAT3 signaling pathways, which is caused by the acute inflammatory response following SCI in different periods via establishing an acute SCI model in rat. Methods. Basso, Beattie, and Bresnahan hind limb locomotor rating scale was used to assess the rat hind limb motor function. Immunohistochemistry was used to determine the expression levels of IL-17 and p-STAT3 in spinal cord tissues. Western blotting analysis was used to determine the protein expression of p-STAT3 in spinal cord tissue. RT-PCR was used to analyze the mRNA expression of IL-17 and IL-23p19 in the spleen tissue. ELISA was used to determine the peripheral blood serum levels of IL-6, IL-21, and IL-23. Results. Compared to the sham-operated group, the expression levels of IL-17, p-STAT3, IL-6, IL-21, and IL-23 were significantly increased and peaked at 24 h after SCI. The increased levels of cytokines were correlated with the SCI disease stages. Conclusion. IL-17 may play an important role in promoting spinal cord neuroinflammation after SCI via activation of STAT3.

miR-136-5p Regulates the Inflammatory Response by Targeting the IKKβ/NF-κB/A20 Pathway After Spinal Cord Injury

“…Bladder compression urination was recorded twice daily. The BBB (Basso, Beattie, and Bresnahan) scoring method [12] (21 levels) was used as a functional assessment to evaluate behavior and hindlimb motor function in the rats before and after SCI. The evaluations were performed before injury and on postoperative days 1, 3, and 7, and each index was measured three times.…”

“…In the resting state, NF-κB binds to its inhibitory monomer (IκB) [9]. The protein remains in the cytoplasm at rest but is activated by SCI in nerve cells, glial cells, and vascular endothelial cells [10][11][12]. Activated NF-κB enters the nucleus and binds to the κB sequence in the promoter or enhancer of the target gene to promote the expression of a large number of inflammatory cytokines, inflammatory chemokines, and adhesion molecules that target gene release, such as IL-1, TNF-α, IL-6, IL-8, and ICAM-1.…”

Clinical implications of leukocyte infiltration at the choroid plexus in (neuro)inflammatory disorders

“…SCI is severe traumatic injury to the spinal cord (SC) that usually results in sensation disability and paralysis [87,93]. There is currently no effective therapy [87].…”

“…Given that the primary injury is always unexpected, the SC can be protected or rescued only during the secondary injury phase [95]. However, the mechanisms underlying secondary injury are not fully defined [93][94][95][96]. Recovery following SCI is impaired in IFN-gR À/À mice, and this impairment is linked to reduced expression of the trafficking molecule ICAM-1 and the chemokines CXCL9 and -10 by the CP, which results in reduced T cell and monocyte entry into the CSF [46].…”

Transplantation or Transference of Cultured Cells as a Treatment for Spinal Cord Injury

“…During acute phase, SC expresses high amounts of Th1 phenotype which is mainly regulated by IL-2, IL-12 and IFNy. Moreover, in subacute phases IL-4, IL-13, IL-10, IL-17 and IL-23 cytokines are found in plasma and spleen, indicating the presence of Th2, Treg and Th17 profiles as an inefficient compensatory mechanism [93,94]. Accordingly to this, for the last 10 years experimental findings have shown that T lymphocytes are not just pathogenic but beneficial.…”