Heme Oxygenase-1 may Mediate Early Inflammatory Response of Intracerebral Hemorrhage through Toll-like Receptor 4 Signaling Pathway.

ABSTRACT

OBJECTIVE: The aim of this study was to investigate whether heme oxygenase-1 (HO-1) promotes an early neuroinflammatory response after intracerebral hemorrhage (ICH) by regulating the toll-like receptor 4 (TLR4) signaling pathway. METHODS: We used a stereotaxic instrument to induce a mouse model of ICH through collagenase. We divided the participants into a control group, an ICH group, and an ICH and zinc protoporphyrin IX (ZnPP) group. The temporal expression pattern and cell localization of HO-1 and TLR4 after the ICH were detected by immunofluorescence and western blot; after the expression of HO-1 was inhibited, the expression levels of the TLR4 protein, the downstream molecule myeloid differentiation factor 88 (MyD88), the Toll and interleukin-1 receptor (TIR) -domain-containing adapter-inducing interferon-ß (TRIF) and the inflammatory factors were measured by western blotting. RESULTS: Immunofluorescence showed that HO-1 and TLR4 had similar temporal expression patterns and cellular localization after ICH, and we found that inhibiting HO-1 reduces the expression of TLR4 protein pathways, including TLR4, MyD88, TRIF, and related inflammatory factors, by studying the inhibitor ZnPP. CONCLUSION: These results indicate that HO-1 may promote early neuroinflammation after ICH through the TLR4/MyD88/TRIF signaling pathway.