title: The cannabinoid receptor CB2 exerts antifibrotic effects in experimental dermal fibrosis.
abstract: OBJECTIVE
  The cannabinoid receptor CB2 is predominantly expressed in non-neuronal tissue and exerts potent immunomodulatory effects. This study was undertaken to evaluate the role of CB2 in the pathogenesis of dermal fibrosis.
  
  
  METHODS
  Mice deficient in CB2 (CB2(-/-) mice) and their wild-type littermates (CB2(+/+) mice) were injected with bleomycin to induce experimental fibrosis. Mice were treated with selective agonists and antagonists of CB2. Lesional skin was evaluated for dermal thickness and numbers of infiltrating leukocytes. Bone marrow transplantation experiments were performed.
  
  
  RESULTS
  CB2(-/-) mice were more sensitive to bleomycin-induced dermal fibrosis than were CB2(+/+) mice, and showed increased dermal thickness. Leukocyte counts were significantly higher in the lesional skin of CB2(+/+) mice. Increased dermal fibrosis was also observed upon treatment with the CB2 antagonist AM-630. In contrast, the selective CB2 agonist JWH-133 reduced leukocyte infiltration and dermal thickening. The phenotype of CB2(-/-) mice was mimicked by transplantation of CB2(-/-) bone marrow into CB2(+/+) mice, whereas CB2(-/-) mice transplanted with bone marrow from CB2(+/+) mice did not display an increased sensitivity to bleomycin-induced fibrosis, indicating that leukocyte expression of CB2 critically influences experimental fibrosis.
  
  
  CONCLUSIONS
  Our findings indicate that CB2 limits leukocyte infiltration and tissue fibrosis in experimental dermal fibrosis. Since selective CB2 agonists are available and well tolerated, CB2 might be an interesting molecular target for the treatment of early inflammatory stages of systemic sclerosis.
authors.affiliation: University of Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Alfiya
authors.initials: A
authors.lastname: Akhmetshina
authors.forename: Clara
authors.initials: C
authors.lastname: Dees
authors.forename: Nicole
authors.initials: N
authors.lastname: Busch
authors.forename: Jürgen
authors.initials: J
authors.lastname: Beer
authors.forename: Kerstin
authors.initials: K
authors.lastname: Sarter
authors.forename: Jochen
authors.initials: J
authors.lastname: Zwerina
authors.forename: Andreas
authors.initials: A
authors.lastname: Zimmer
authors.forename: Oliver
authors.initials: O
authors.lastname: Distler
authors.forename: Georg
authors.initials: G
authors.lastname: Schett
authors.forename: Jörg H W
authors.initials: JH
authors.lastname: Distler