Effects of JWH015 in cytokine secretionin primary human keratinocytes andfibroblasts and its suitability fortopical/transdermal delivery
Authors
Bort Bueno, Alicia Carmen; Alvarado Vazquez, Perla Avigail; Moracho Vilrriales, Carolina; Virga, Kristopher Carey; Gumina, Giuseppe; [et al.]Identifiers
Permanent link (URI): http://hdl.handle.net/10017/60103DOI: 10.1177/1744806916688220
ISSN: 1744-8069
Date
2016-12-07Bibliographic citation
Molecular Pain, 2016, v. 13, p. 1-16
Keywords
Cannabinoid receptors
JWH015
cytokine
fibroblasts
keratinocytes
Project
IACP grant 2016 (SA). Rita Allen Foundation & American Pain Society 2011 Pain Grant (AR-S); NIH/NIGMS, R15GM109333 (AR-S).
Document type
info:eu-repo/semantics/article
Version
info:eu-repo/semantics/publishedVersion
Rights
© The Author(s) 2017
Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)
Access rights
info:eu-repo/semantics/openAccess
Abstract
Background JWH015 is a cannabinoid (CB) receptor type 2 agonist that produces immunomodulatory effects. Since skin cells play a key role in inflammatory conditions and tissue repair, we investigated the ability of JWH015 to promote an anti-inflammatory and pro-wound healing phenotype in human primary skin cells. MethodsHuman primary keratinocytes and fibroblasts were stimulated with lipopolysaccharide. The mRNA expression of cannabinoid receptors was determined using RT-PCR. The effects of JWH015 (0.05, 0.1, 0.5, and 1?µM) in pro- and anti-inflammatory factors were tested in lipopolysaccharide-stimulated cells. A scratch assay, using a co-culture of keratinocytes and fibroblasts, was used to test the effects of JWH015 in wound healing. In addition, the topical and transdermal penetration of JWH015 was studied in Franz diffusion cells using porcine skin and LC-MS. Results The expression of CB1 and CB2 receptors (mRNA) and the production of pro- and anti-inflammatory factors enhanced in keratinocytes and fibroblasts following lipopolysaccharide stimulation. JWH015 reduced the concentration of major pro-inflammatory factors (IL-6 and MCP-1) and increased the concentration of a major anti-inflammatory factor (TGF-?) in lipopolysaccharide-stimulated cells. JWH015 induced a faster scratch gap closure. These JWH015?seffects were mainly modulated through both CB1 and CB2 receptors. Topically administered JWH015 was mostly retained in the skin and displayed a sustained and low level of transdermal permeation. Conclusions Our findings suggest that targeting keratinocytes and fibroblasts with cannabinoid drugs could represent a therapeutic strategy to resolve peripheral inflammation and promote tissue repair.
Files in this item
Files | Size | Format |
|
---|---|---|---|
Effects_Bort_MolPain_2017.pdf | 882.0Kb |
|
Files | Size | Format |
|
---|---|---|---|
Effects_Bort_MolPain_2017.pdf | 882.0Kb |
|
Collections
- BIOQBM - Artículos [137]