Involvement of TLR2/4-MyD88-NF-kappa B signaling pathway in the pathogenesis of intracranial aneurysm

Toll-like receptor (TLR) 2/4 serves an important regulatory role in nerve tissue injury. However, the downstream and potential mechanisms remain to be elucidated. The present study was designed to investigate the roles of the TLR2/4-major myeloid differentiation response gene 88 (MyD88)-NF-kappa B signaling pathway in the development of intracranial aneurysm. The expression of TLR2, TLR4 and MyD88 in the blood of normal controls and patients with intracranial aneurysm were detected by quantitative PCR and ELISA. Human brain vascular smooth muscle cells were treated by Angiotensin II (Ang II) to evaluate the involvement of TLR2/4-MyD88-NF-kappa B signaling pathway in the process. The in vitro experiment was divided into four groups: The control group, an Ang II group, an Ang II + small interfering (si)RNA control group and an Ang II + TLR2-group. Cell viability, migration, apoptosis and expression of TLR2, TLR4, MyD88, NF-kappa B and phosphorylated (p-)p65 expression were detected. The results demonstrated that the expression of TLR2, TLR4, MyD88 and NF-kappa B at mRNA and protein levels in patients with intracranial aneurysm was significantly higher compared with corresponding protein in normal controls (P