The role of the endocannabinoid system in the regulation of cellular immune responses in the skin
Final Report Abstract
G-protein coupled cannabinoid receptors (CB1 and CB2), endogenous lipid ligands (endocannabinoids) and the enzymatic machinery involved in their synthesis and degradation constitute the “endocannabinoid system” (ECS). Using pharmacological and genetic approaches to block CB receptor signaling, we demonstrated that the ECS attenuates allergic inflammation in experimental models for contact allergy and atopic dermatitis. In particular, our observations reveal a previously unrecognized physiological role of CB1 receptors on keratinocytes for the maintenance of epidermal integrity and permeability barrier functions by endocannabinoids which contributes to the protection against contact allergic inflammation. These findings could open up new strategies for the topical treatment of inflammatory skin diseases with the help of antiinflammatory lipids, including cannabinoids.
Publications
- Early onset of aging-like changes is restricted to cognitive abilities and skin structure in Cnr1−/− mice. Neurobiol Aging. 2012 Jan;33(1):200.e11-22
Bilkei-Gorzo A, Drews E, Albayram Ö, Piyanova A, Gaffal E, Tüting T, Michel K, Mauer D, Maier W, ZImmer A
(See online at https://doi.org/10.1016/j.neurobiolaging.2010.07.009) - Anti-inflammatory activity of topical THC in DNFB-mediated mouse allergic contact dermatitis independent of CB1 and CB2 receptors. Allergy. 2013 Aug;68(8):994-1000
Gaffal E, Cron M, Glodde N, Tüting T
(See online at https://doi.org/10.1111/all.12183) - Cannabinoid 1 receptors in keratinocytes modulate proinflammatory chemokine secretion and attenuate contact allergic inflammation. J Immunol. 2013 May 15;190(10):4929-36
Gaffal E, Cron M, Glodde N, Bald T, Kuner R, Zimmer A, Lutz B, Tüting T
(See online at https://doi.org/10.4049/jimmunol.1201777) - Cannabinoid 1 receptors in keratinocytes attenuate FITC-induced mouse atopic-like dermatitis. Exp Dermatol. 2014 Jun;23(6):401-6
Gaffal E, Glodde N, Jakobs M, Bald T, Tüting T
(See online at https://doi.org/10.1111/exd.12414) - Differential role of cannabinoids in the pathogenesis of skin cancer. Life Sci. 2015 Oct 1;138:35-40. (IF: 2.70)
Glodde N, Jakobs M, Bald T, Tüting T, Gaffal E
(See online at https://doi.org/10.1016/j.lfs.2015.04.003)