Cannabinoid receptor 2 deficiency exacerbates inflammation and neutrophil recruitment.

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
Theodore S KapellosAsif J Iqbal

Abstract

Cannabinoid receptor (CB)2 is an immune cell-localized GPCR that has been hypothesized to regulate the magnitude of inflammatory responses. However, there is currently no consensus as to the mechanism by which CB2 mediates its anti-inflammatory effects in vivo. To address this question, we employed a murine dorsal air pouch model with wild-type and CB2-/- 8-12-wk-old female and male C57BL/6 mice and found that acute neutrophil and lymphocyte antigen 6 complex, locus Chi monocyte recruitment in response to Zymosan was significantly enhanced in CB2-/- mice. Additionally, levels of matrix metalloproteinase 9 and the chemokines C-C motif chemokine ligand (CCL)2, CCL4, and C-X-C motif chemokine ligand 10 in CB2-/- pouch exudates were elevated at earlier time points. Importantly, using mixed bone marrow chimeras, we revealed that the proinflammatory phenotype in CB2-/- mice is neutrophil-intrinsic rather than stromal cell-dependent. Indeed, neutrophils isolated from CB2-/- mice exhibited an enhanced migration-related transcriptional profile and increased adhesive phenotype, and treatment of human neutrophils with a CB2 agonist blocked their endothelial transmigration. Overall, we have demonstrated that CB2 plays a nonredundant role d...Continue Reading

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Citations

Apr 21, 2019·International Journal of Molecular Sciences·Francesca RossiSilverio Perrotta
Sep 19, 2019·DNA and Cell Biology·Mohammed Tayab HussainAsif Jilani Iqbal
Aug 29, 2019·Journal of Clinical Periodontology·Chunyan LiuZheng Zhou
Jul 18, 2020·Journal of Dietary Supplements·Elnaz Karimian AzariAnnalouise O'Connor
Jun 27, 2020·International Journal of Molecular Sciences·Osnat Almogi-Hazan, Reuven Or
Apr 25, 2019·International Journal of Molecular Sciences·Alex Mabou TagneMarco Cosentino
Oct 20, 2020·Frontiers in Immunology·Noah FineMichael Glogauer
Nov 11, 2020·British Journal of Pharmacology·Alireza TahamtanVahid Salimi
Mar 2, 2021·Frontiers in Immunology·Nicole PalandIgal Louria-Hayon
Feb 18, 2021·British Journal of Pharmacology·Federica RaucciFrancesco Maione
May 1, 2021·International Journal of Molecular Sciences·Estefanía MorenoEnric I Canela
Jul 30, 2021·ImmunoTargets and Therapy·Valeria GiorgiPiercarlo Sarzi-Puttini
Aug 10, 2021·Current Protocols·Jill C Fehrenbacher, Kenneth E McCarson

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Methods Mentioned

BETA
PCR
fluorescence-activated cell sorting
FACS
flow cytometry
ELISA
FCS
transgenic

Software Mentioned

R
Image Pro
Prism
nCounter
GraphPad
FlowJo
NanoStringDiff

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