Research Paper Volume 12, Issue 14 pp 14849—14862
Targeting CCL20 inhibits subarachnoid hemorrhage-related neuroinflammation in mice
- 1 Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
- 2 Department of Neurosurgery, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou 646000, China
Received: March 4, 2020 Accepted: June 4, 2020 Published: June 21, 2020https://doi.org/10.18632/aging.103548
How to Cite
Copyright © 2020 Liao et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Recent evidence suggests that CC chemokine ligand 20 (CCL20) is upregulated after subarachnoid hemorrhage (SAH). Here, we investigated the functions of CCL20 in SAH injury and its underlying mechanisms of action. We found that CCL20 is upregulated in an SAH mouse model and in cultured primary microglia and neurons. CCL20-neutralizing antibody alleviated SAH-induced neurological deficits, decreased brain water content and neuronal apoptosis, and repressed microglial activation. We observed increased levels of CCL20, CC chemokine receptor 6 (CCR6), interleukin 1 beta (IL-1β), and tumor necrosis factor alpha (TNF-α), as well as of microglial activation in microglia treated with oxyhemoglobin (OxyHb). CCL20 or CCR6 knockdown reversed the effects of OxyHb on microglia. Conditioned medium from OxyHb-treated microglia induced neuronal apoptosis, while the percentage of apoptotic neurons in the conditioned medium from microglia transfected with CCL20 siRNA or CCR6 siRNA was decreased. We observed no decrease in OxyHb-induced apoptosis in CCL20-knockdown neurons. Conditioned medium from OxyHb-treated neurons led to microglial activation and induced CCR6, IL-1β and TNF-α expression, while CCL20 knockdown in neurons or CCR6 knockdown in microglia reversed those effects. Our results thus suggest CCL20 may be targeted to elicit therapeutic benefits after SAH injury.
ACA: anterior cerebral artery; BBB: blood-brain barrier; BSA: bovine serum albumin; CCL20: CC chemokine ligand 20; CCR6: CC chemokine receptor 6; EBI: early brain injury; ELISA: Enzyme-linked immunosorbent assay; ICA: internal carotid artery; IL-1β: interleukin 1 beta; LARC: liver and activation-regulated chemokine; MCA: middle cerebral artery; OxyHb: oxyhemoglobin; RT-qPCR: reverse transcription quantitative polymerase chain reaction; SAH: subarachnoid hemorrhage; siRNA: Small interfering RNA; TNF-α: tumor necrosis factor alpha; TUNEL: terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling.