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Sult2b1 deficiency exacerbates ischemic stroke by promoting pro-inflammatory macrophage polarization in mice
- Source :
- Theranostics
- Publication Year :
- 2021
- Publisher :
- Ivyspring International Publisher, 2021.
-
Abstract
- Rationale: Stroke is a leading causes of human death worldwide. Ischemic damage induces the sterile neuroinflammation, which directly determines the recovery of patients. Lipids, a major component of the brain, significantly altered after stroke. Cholesterol sulfate, a naturally occurring analog of cholesterol, can directly regulate immune cell activation, indicating the possible involvement of cholesterol metabolites in neuroinflammation. Sulfotransferase family 2b member 1 (Sult2b1) is the key enzyme that catalyzes the synthesis of cholesterol sulfate. This study aimed to investigate the function of Sult2b1 and cholesterol sulfate in the neuroinflammation after ischemic stroke. Methods and Results: Sult2b1-/- and wild-type mice were subjected to transient middle cerebral artery occlusion. Our data showed that Sult2b1-/- mice had larger infarction and worse neurological scores. To determine whether immune cells were involved in the worsening stroke outcome in Sult2b1-/- mice, bone marrow transplantation, immune cell depletion, and adoptive monocyte transfer were performed. Combined with CyTOF and immunofluorescence techniques, we demonstrated that after stroke, the peripheral monocyte-derived macrophages were the dominant cell type promoting the pro-inflammatory status in Sult2b1-/-mice. Using primary bone marrow-derived macrophages, we showed that cholesterol sulfate could attenuate the pro-inflammatory polarization of macrophages under both normal and oxygen-glucose deprivation conditions by regulating the levels of nicotinamide adenine dinucleotide phosphate (NADPH), reactive oxygen species (ROS), and activating the AMP-activated protein kinase (AMPK) - cAMP responsive element-binding protein (CREB) signaling pathway. Conclusions: Sult2b1-/- promoted the polarization of macrophages into pro-inflammatory status. This trend could be attenuated by adding cholesterol sulfate, which promotes the polarization of macrophages into anti-inflammatory status by metabolic regulation. In this study, we established an inflammation-metabolism axis during the macrophage polarization after ischemic stroke.
- Subjects :
- Male
medicine.medical_specialty
Macrophage
Macrophage polarization
Medicine (miscellaneous)
Sult2b1
Cholesterol Sulfate
Monocytes
Brain Ischemia
chemistry.chemical_compound
Mice
Immune system
Neuroinflammation
Internal medicine
SULT2B1
Medicine
Animals
Humans
Pharmacology, Toxicology and Pharmaceutics (miscellaneous)
Stroke
Ischemic Stroke
Inflammation
Mice, Knockout
business.industry
Cholesterol
Monocyte
Macrophages
Infarction, Middle Cerebral Artery
Recovery of Function
Macrophage Activation
medicine.disease
Mice, Inbred C57BL
Disease Models, Animal
medicine.anatomical_structure
Endocrinology
chemistry
Neuroinflammatory Diseases
Cholesterol Esters
Microglia
Sulfotransferases
business
Nicotinamide adenine dinucleotide phosphate
Research Paper
Signal Transduction
Subjects
Details
- Language :
- English
- ISSN :
- 18387640
- Volume :
- 11
- Issue :
- 20
- Database :
- OpenAIRE
- Journal :
- Theranostics
- Accession number :
- edsair.doi.dedup.....a1d0eabaee6e0a60db5302e7b4a5623d