Abstract / Summary
Abstract Background Neuroinflammation and myelin dysfunction are core pathological features of bipolar disorder (BD). Interleukin-17 (IL-17), a key pro-inflammatory cytokine, is elevated in patients with mood disorders, but its direct effect on oligodendrocyte myelination and the underlying mechanism remain unclear. Methods Human oligodendrocyte cell line MO3.13 was treated with IL-17, and the expression of myelin-related proteins (MBP, PLP1, CNPase) was detected by qPCR, Western blot, and immunofluorescence staining. The activation of the NF-κB/STAT3 pathway was evaluated by measuring the phosphorylation levels of NF-κB p65 and STAT3. Pathway inhibitors (BAY11-7082 for NF-κB, Stattic for STAT3) were used to verify the mediating role of the pathway. Results IL-17 significantly downregulated the mRNA and protein levels of MBP, PLP1, and CNPase in MO3.13 cells (****p < 0.0001). Mechanistically, IL-17 increased the phosphorylation of NF-κB p65 (Ser536) and STAT3 (Tyr705) without altering their total protein or mRNA expression. Pretreatment with BAY11-7082 or Stattic markedly reversed IL-17-induced myelin-related protein suppression and pathway activation (####p < 0.0001). Conclusion IL-17 inhibits myelin-related protein expression in human oligodendrocytes via activating the NF-κB/STAT3 signaling pathway. These findings provide a mechanistic link between neuroinflammation and myelin damage in bipolar disorder and highlight the IL-17/NF-κB/STAT3 axis as a translational therapeutic target.