VSIG4 alleviates intracerebral hemorrhage induced brain injury by suppressing TLR4-regulated inflammatory response

Aims: Numerous evidence demonstrated that macrophage mediated inflammation contributed to brain injury following ICH, but the molecular mechanism had not been well studied. V-set immunoglobulin-domain-containing 4 (VSIG4), specifically expresses in resting tissue-resident macrophages, can deliver antiinflammatory signals into various inflammatory diseases. However, the role of VSIG4 on ICH has not been reported. Methods: In the present study, we investigated the levels of VSIG4 in macrophages following ICH. Furthermore, Macrophage M1/M2 polarization, pro-inflammatory cytokine production, BBB disruption, brain water content and neurological function were examined in ICH mice. In addition, TLR4/NF-kappa beta downstream signals were also analyzed. Results: The results showed that VSIG4 levels of macrophage decreased following ICH, leading to macrophage M1 polarization. Up-regulation of VSIG4 inhibited macrophage M1 polarization, pro-inflammatory cytokine production, BBB disruption, as well as neurological deficits. Up-regulation of VSIG4 attenuated macrophage TLR4 levels following ICH. Co-IP demonstrated that VSIG4 could interact with TLR4 and inhibit its expression. Conclusions: Our data demonstrated that VSIG4 was negatively correlated with TLR4 and involved in the pathogenesis of ICH, which prevented brain injury and attenuated deleterious inflammatory responses following ICH. In addition, the anti-inflammatory effect of VSIG4 was mainly through the blockage of TLR4/NF-kappa beta signaling.

Automated summary

This study found that levels of VSIG4 in macrophages decreased after intracerebral hemorrhage, leading to macrophage M1 polarization. Up-regulation of VSIG4 inhibited macrophage M1 polarization, pro-inflammatory cytokine production, BBB disruption, and neurological deficits following ICH. Additionally, the anti-inflammatory effect of VSIG4 was mainly through blocking TLR4/NF-kappa beta signaling.