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-β (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.
Keywords: Heme oxygenase-1, toll-like receptor 4, intracerebral hemorrhage, microglia, inflammation, neuroinflammation.
[http://dx.doi.org/10.1038/nrneurol.2017.69] [PMID: 28524175]
[http://dx.doi.org/10.1161/STROKEAHA.117.017358] [PMID: 28663510]
[http://dx.doi.org/10.1007/s12035-016-9785-6] [PMID: 26894396]
[http://dx.doi.org/10.1016/S0140-6736(18)31878-6] [PMID: 30319113]
[http://dx.doi.org/10.1177/0271678X16655814] [PMID: 27317654]
[http://dx.doi.org/10.1007/s12035-016-0271-y] [PMID: 27864733]
[http://dx.doi.org/10.1093/brain/awm095] [PMID: 17525142]
[http://dx.doi.org/10.1186/1742-2094-9-46] [PMID: 22394415]
[http://dx.doi.org/10.1002/ana.22528] [PMID: 22028224]
[http://dx.doi.org/10.1177/0271678X18815791] [PMID: 30516406]
[http://dx.doi.org/10.1186/s12974-019-1485-5] [PMID: 31072336]
[http://dx.doi.org/10.1016/j.bbi.2016.12.012] [PMID: 28007523]
[http://dx.doi.org/10.1161/CIRCULATIONAHA.116.021881] [PMID: 27576776]
[http://dx.doi.org/10.1038/nrneurol.2015.226] [PMID: 26670299]
[http://dx.doi.org/10.1038/nrneurol.2014.264] [PMID: 25623787]
[http://dx.doi.org/10.1136/bmj.h2484] [PMID: 25994363]
[http://dx.doi.org/10.18632/aging.103343] [PMID: 32602850]
[http://dx.doi.org/10.3390/vaccines5040034] [PMID: 28976923]
[http://dx.doi.org/10.1152/ajprenal.00432.2017] [PMID: 28978536]
[http://dx.doi.org/10.1016/j.freeradbiomed.2019.04.024] [PMID: 31026585]
[http://dx.doi.org/10.1016/j.jneuroim.2015.10.006] [PMID: 26616876]