Anti-inflammatory effects of lenabasum, a cannabinoid receptor type 2 agonist, on macrophages from cystic fibrosis. Tarique, AA, Evron, T, Zhang, G, Tepper, MA, Morshed, MM, Andersen, ISG, Begum, N, Sly, Peter and Fantino, E 2020, Anti-inflammatory effects of lenabasum, a cannabinoid receptor type 2 agonist, on macrophages from cystic fibrosis., J Cyst Fibros, vol. 19, no. 5, pp. 823-829, doi: 10.1016/j.jcf.2020.03.015. Attached Files Name Description MIMEType Size Downloads Title Anti-inflammatory effects of lenabasum, a cannabinoid receptor type 2 agonist, on macrophages from cystic fibrosis. Author(s) Tarique, AA Evron, T Zhang, G Tepper, MA Morshed, MM Andersen, ISG Begum, N Sly, Peter Fantino, E Journal name J Cyst Fibros Volume number 19 Issue number 5 Start page 823 End page 829 Total pages 7 Publisher p Place of publication Netherlands Publication date 2020-09 ISSN 1873-5010 Keyword(s) Science & Technology Life Sciences & Biomedicine Respiratory System Cystic fibrosis Macrophage responses Macrophage polarization Cannabinoid 2 receptor (CB2) CB2 agonists Phagocytosis Endocytosis Anti-inflammatory RECRUITED MONOCYTES LUNG-DISEASE INFLAMMATION INFANTS CELLS ACTIVATION CHILDREN CA2+ Summary BACKGROUND: Lenabasum is an oral synthetic cannabinoid receptor type 2 agonist previously shown to reduce the production of key airway pro-inflammatory cytokines known to play a role in cystic fibrosis (CF). In a double-blinded, randomized, placebo-control phase 2 study, lenabasum lowered the rate of pulmonary exacerbation among patients with CF. The present study was undertaken to investigate anti-inflammatory mechanisms of lenabasum exhibits in CF macrophages. METHODS: We used monocyte-derived macrophages (MDMs) from healthy donors (n = 15), MDMs with CFTR inhibited with C-172 (n = 5) and MDMs from patients with CF (n = 4). Monocytes were differentiated to macrophages and polarized into classically activated (M1) macrophages by LPS or alternatively activated (M2) macrophages by IL-13 in presence or absence of lenabasum. RESULTS: Lenabasum had no effect on differentiation, polarization and function of macrophages from healthy individuals. However, in CF macrophages lenabasum downregulated macrophage polarization into the pro-inflammatory M1 phenotype and secretion of the pro-inflammatory cytokines IL-8 and TNF-α in a dose-dependent manner. An improvement in phagocytic activity was also observed following lenabasum treatment. Although lenabasum did not restore the impaired polarization of anti-inflammatory M2 macrophage, it reduced the levels of IL-13 and enhanced the endocytic function of CF MDMs. The effects of lenabasum on MDMs with CFTR inhibited by C-172 were not as obvious. CONCLUSION: In CF macrophages lenabasum modulates macrophage polarization and function in vitro in a way that would reduce inflammation in vivo. Further studies are warranted to determine the link between activating the CBR2 receptor and CFTR. Language eng DOI 10.1016/j.jcf.2020.03.015 Indigenous content off Field of Research 1103 Clinical Sciences Persistent URL http://hdl.handle.net/10536/DRO/DU:30164616 Document type: Journal Article Collections: Faculty of Health School of Psychology Related Links Link Description Connect to published version Go to link with your DU access privileges   Author URL Go to link with your DU access privileges   Connect to Elements publication management system Go to link with your DU access privileges     Unless expressly stated otherwise, the copyright for items in DRO is owned by the author, with all rights reserved. Versions Version Filter Type Fri, 18 Mar 2022, 07:34:42 EST Fri, 18 Mar 2022, 15:58:53 EST Wed, 06 Apr 2022, 08:59:00 EST Thu, 21 Apr 2022, 16:56:07 EST Fri, 22 Apr 2022, 12:19:46 EST Filtered Full Citation counts:   Cited 5 times in TR Web of Science Cited 5 times in Scopus Search Google Scholar Access Statistics: 5 Abstract Views, 0 File Downloads  -  Detailed Statistics Created: Fri, 18 Mar 2022, 07:34:42 EST