Quick Search:

uzh logo
Browse by:

Zurich Open Repository and Archive

Maintenance: Tuesday, July the 26th 2016, 07:00-10:00

ZORA's new graphical user interface will be relaunched (For further infos watch out slideshow ZORA: Neues Look & Feel). There will be short interrupts on ZORA Service between 07:00am and 10:00 am. Please be patient.

Marquart, S; Zerr, P; Akhmetshina, A; Palumbo, K; Reich, N; Tomcik, M; Horn, A; Dees, C; Engel, M; Zwerina, J; Distler, O; Schett, G; Distler, J H W (2010). Inactivation of the cannabinoid receptor CB1 prevents leukocyte infiltration and experimental fibrosis. Arthritis and Rheumatism, 62(11):3467-3476.

Full text not available from this repository.

View at publisher


OBJECTIVE: Cannabinoids are derivates of the marijuana component Δ(9) -tetrahydrocannabinol that exert their effects on mesenchymal cells and immune cells via CB1 and CB2 receptors. The aim of the present study was to evaluate the role of CB1 in systemic sclerosis.

METHODS: CB1-deficient (CB1(-/-) ) mice and wild-type littermates (CB1(+/+) mice) were injected with bleomycin. CB1 signaling was activated in vivo with the selective agonist N-(2-chloroethyl)-5Z,8Z,11Z,14Z-eicosatetraenamide (ACEA). Bone marrow transplantation experiments were performed to investigate whether the phenotype of CB1(-/-) mice was mediated by leukocytes or mesenchymal cells. The role of CB1 was also investigated in the TSK-1 mouse model.

RESULTS: CB1(-/-) mice were protected from bleomycin-induced dermal fibrosis, with reduced dermal thickening, hydroxyproline content, and myofibroblast counts. Inactivation of CB1 decreased the number of infiltrating T cells and macrophages in lesional skin. In contrast, activation of CB1 with ACEA increased leukocyte infiltration and enhanced the fibrotic response to bleomycin. The phenotype of CB1(-/-) mice was mimicked by transplantation of CB1(-/-) mouse bone marrow into CB1(+/+) mice, demonstrating that CB1 exerts its profibrotic effects indirectly by regulating leukocyte infiltration. Consistently, knockdown of CB1 did not prevent fibrosis in the inflammation-independent TSK-1 mouse model.

CONCLUSION: We demonstrate that the cannabinoid receptor CB1 is crucial for leukocyte infiltration and secondary fibroblast activation and that inactivation of CB1 exerts potent antifibrotic effects in inflammation-driven models of fibrosis.
Copyright © 2010 by the American College of Rheumatology.


20 citations in Web of Science®
20 citations in Scopus®
Google Scholar™


Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Rheumatology Clinic and Institute of Physical Medicine
Dewey Decimal Classification:610 Medicine & health
Deposited On:02 Feb 2011 16:51
Last Modified:05 Apr 2016 14:40
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:10.1002/art.27642
PubMed ID:20617520

Users (please log in): suggest update or correction for this item

Repository Staff Only: item control page