IMM-H004 protects against oxygen-glucose deprivation/reperfusion injury to BV2 microglia partly by modulating CKLF1 involved in microglia polarization.

Abstract

BACKGROUND:

IMM-H004 is a novel compound that has been shown to protect against cerebral ischemia/reperfusion injury in our previous works. Chemokine-like factor 1 (CKLF1) is a chemokine that exhibits increased expression in the ischemic brain. Dysregulation of microglia polarization dynamics is a mechanism of injury expansion poststroke.

PURPOSES:

The aim of present study was to investigate the effects of IMM-H004 on cell viability and microglia phenotypes in BV2 microglia suffering from oxygen-glucose deprivation/reperfusion and discussing the involvement of CKLF1 and possible mechanisms.

RESULTS:

IMM-H004 protected BV2 microglia from oxygen-glucose deprivation/reperfusion-induced toxicity. We found that the expression of CKLF1 was increased in BV2 microglia with oxygen-glucose deprivation/reperfusion, and IMM-H004 decreased this specially increased expression. Moreover, oxygen-glucose deprivation/reperfusion induced the BV2 microglia to polarize toward an M1 phenotype, and IMM-H004 modulated the polarization shift from the M1 phenotype and skewed toward the M2 phenotype, followed by suppressing the excessive inflammatory response and improving recovery. CKLF1 modulated BV2 microglia toward M1 polarization and induced an inflammatory response. By using receptor inhibitors, we found that OGD/R induced microglia polarization partly through CC chemokine receptor 4. Furthermore, the Co-IP assay showed that IMM-H004 decreased the amount of CKLF1 binding to CC chemokine receptor 4 in the BV2 microglia oxygen-glucose deprivation/reperfusion model.

CONCLUSIONS:

IMM-H004 protects BV2 microglia against oxygen-glucose deprivation/reperfusion injury partly by modulating microglia polarization and further regulating the inflammatory response. The CKLF1/CCR4 axis may be involved in the protective effects of IMM-H004 modulating microglia polarization.

• Authors: Chen Chen, Qidi Ai, Shifeng Chu, Zhao Zhang, Xin Zhou, Piao Luo, Yingjiao Liu, Naihong Chen
• Journal: International immunopharmacology (Int Immunopharmacol) Vol. 70 Pg. 69-79 (May 2019) ISSN: 1878-1705 [Electronic] Netherlands
• PMID: 30785093 (Publication Type: Journal Article)
• Copyright: Copyright © 2019. Published by Elsevier B.V.

Chemical References

• Ccr4 protein, rat
• Chemokines
• Cklf protein, rat
• Coumarins
• Cytokines
• IMM-H004
• MARVEL Domain-Containing Proteins
• Neuroprotective Agents
• Receptors, CCR4
• Glucose
• Oxygen

Topics

• Animals
• Cell Differentiation
• Cell Line
• Cell Survival (drug effects)
• Chemokines (metabolism)
• Coumarins (pharmacology)
• Cytokines (metabolism)
• Glucose (metabolism)
• MARVEL Domain-Containing Proteins (metabolism)
• Microglia (drug effects, pathology)
• Neuroprotective Agents (pharmacology)
• Oxygen (metabolism)
• Rats
• Receptors, CCR4 (metabolism)
• Reperfusion Injury (drug therapy)
• Th1 Cells (immunology)