Next Article in Journal
Excess TPX2 Interferes with Microtubule Disassembly and Nuclei Reformation at Mitotic Exit
Previous Article in Journal
Fibroblasts from the Human Skin Dermo-Hypodermal Junction are Distinct from Dermal Papillary and Reticular Fibroblasts and from Mesenchymal Stem Cells and Exhibit a Specific Molecular Profile Related to Extracellular Matrix Organization and Modeling
Previous Article in Special Issue
Neutrophil Extracellular Traps and Cardiovascular Diseases: An Update
Open AccessArticle

Neutrophil Chemotaxis and NETosis in Murine Chronic Liver Injury via Cannabinoid Receptor 1/ Gαi/o/ ROS/ p38 MAPK Signaling Pathway

Department of Cell Biology, Municipal Laboratory for Liver Protection and Regulation of Regeneration, Capital Medical University, Beijing 100069, China
*
Author to whom correspondence should be addressed.
These authors contributed equally.
Cells 2020, 9(2), 373; https://doi.org/10.3390/cells9020373
Received: 22 January 2020 / Accepted: 3 February 2020 / Published: 5 February 2020
Neutrophils play an essential role in the control of inflammatory diseases. However, whether cannabinoid receptors (CBs) play a role in neutrophil chemotaxis and NETosis in sterile liver inflammation remains unknown. The expression of marker genes on neutrophils was characterized by FACS, immunofluorescence, qRT-PCR, and Western blot. The amount of neutrophils was significantly elevated from 7 days and reached the peak at 2 weeks in carbon tetrachloride (CCl4)-treated mouse liver. The mRNA expression of neutrophil marker Ly6G had positive correlation with CB1 and CB2 expression in injured liver. In vitro CBs were abundantly expressed in isolated neutrophils and CB1 agonist ACEA promoted the chemotaxis and cytoskeletal remodeling, which can be suppressed by CB1 antagonist AM281. Moreover, ACEA induced NETosis, myeloperoxidase release from lysosome and ROS burst, indicating neutrophil activation, via Gαi/o. Conversely, CB2 agonist JWH133 had no effect on neutrophil function. ROS and p38 MAPK signaling pathways were involved in CB1-mediated neutrophil function, and ROS was upstream of p38 MAPK. CB1 blockade in vivo significantly attenuated neutrophil infiltration and liver inflammation in CCl4-treated mice. Taken together, CB1 mediates neutrophil chemotaxis and NETosis via Gαi/o/ROS/p38 MAPK signaling pathway in liver inflammation, which represents an effective therapeutic strategy for liver diseases.
Keywords: liver injury; neutrophil extracellular trap; myeloperoxidase; carbon tetrachloride liver injury; neutrophil extracellular trap; myeloperoxidase; carbon tetrachloride
MDPI and ACS Style

Zhou, X.; Yang, L.; Fan, X.; Zhao, X.; Chang, N.; Yang, L.; Li, L. Neutrophil Chemotaxis and NETosis in Murine Chronic Liver Injury via Cannabinoid Receptor 1/ Gαi/o/ ROS/ p38 MAPK Signaling Pathway. Cells 2020, 9, 373.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop