NADPH oxidase isoform expression is temporally regulated and may contribute to microglial/macrophage polarization after spinal cord injury.

Abstract

Spinal cord injury (SCI) results in both acute and chronic inflammation, as a result of activation of microglia, invasion of macrophages and activation of the NADPH oxidase (NOX) enzyme. The NOX enzyme is a primary source of reactive oxygen species (ROS) and is expressed by microglia and macrophages after SCI. These cells can assume either a pro- (M1) or anti-inflammatory (M2) polarization phenotype and contribute to tissue response to SCI. However, the contribution of NOX expression and ROS production to this polarization and vice versa is currently undefined. We therefore investigated the impact of SCI on NOX expression and microglial/macrophage polarization over time in a mouse model of contusion injury. Adult C57Bl/6 mice were exposed to a moderate T9 contusion SCI and tissue was assessed at acute, sub-acute and chronic time points for NOX isoform expression and co-expression with M1 and M2 microglia/macrophage polarization markers. Two NOX isoforms were increased after injury and were associated with both M1 and M2 markers, with an M1 preference for NOX2 acutely and NOX4 chronically. M2 cells were primarily found at acute time points only; the peak of NOX2 expression was associated with the decline in M2 polarization. In vitro, NOX2 inhibition shifted microglial polarization toward the M2 phenotype. These results now show that microglial/macrophage expression of NOX isoforms is independent of polarization state, but that NOX activity can influence subsequent polarization. These data can contribute to the therapeutic targeting of NOX as a therapy for SCI.

• Authors: Sara Bermudez, Guzal Khayrullina, Yujia Zhao, Kimberly R Byrnes
• Journal: Molecular and cellular neurosciences (Mol Cell Neurosci) Vol. 77 Pg. 53-64 (12 2016) ISSN: 1095-9327 [Electronic] United States
• PMID: 27729244 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Published by Elsevier Inc.

Chemical References

• Cybb protein, mouse
• NADPH Oxidase 2
• NADPH Oxidase 4
• Nox4 protein, mouse

Topics

• Animals
• Cell Differentiation
• Cells, Cultured
• Macrophages (cytology, metabolism)
• Male
• Mice
• Mice, Inbred C57BL
• Microglia (cytology, metabolism)
• NADPH Oxidase 2 (antagonists & inhibitors, genetics, metabolism)
• NADPH Oxidase 4 (genetics, metabolism)
• Spinal Cord Injuries (genetics, metabolism, pathology)