IMM-H004 protects against oxygen-glucose deprivation/reperfusion injury to BV2 microglia partly by modulating CKLF1 involved in microglia polarization
| Autor: | Shifeng Chu, Qi-di Ai, Nai-hong Chen, Chen Chen, Piao Luo, Yingjiao Liu, Xin Zhou, Zhao Zhang |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Chemokine Receptors CCR4 Cell Survival Immunology CCR4 Ischemia Cell Line 03 medical and health sciences Chemokine receptor 0302 clinical medicine Coumarins medicine Animals Immunology and Allergy Viability assay Receptor Pharmacology MARVEL Domain-Containing Proteins biology Microglia Chemistry Cell Differentiation Th1 Cells medicine.disease Rats Cell biology Oxygen Glucose Neuroprotective Agents 030104 developmental biology medicine.anatomical_structure nervous system Reperfusion Injury 030220 oncology & carcinogenesis biology.protein Cytokines Chemokines Reperfusion injury |
| Zdroj: | International Immunopharmacology. 70:69-79 |
| ISSN: | 1567-5769 |
| Popis: | 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 C C chemokine receptor 4. Furthermore, the Co-IP assay showed that IMM-H004 decreased the amount of CKLF1 binding to C C 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. |
| Databáze: | OpenAIRE |
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