Cell type-specific regulatory effects of glucocorticoids on cutaneous TLR2 expression and signalling.
J Steroid Biochem Mol Biol
; 171: 201-208, 2017 07.
Article
in En
| MEDLINE
| ID: mdl-28377308
ABSTRACT
Glucocorticoids (GCs) induce Toll-like receptor (TLR) 2 expression and synergistically upregulate TLR2 with pro-inflammatory cytokines or bacteria. These paradoxical effects have drawn attention to the inflammatory initiating or promoting effects of GCs, as GC treatment can provoke inflammatory skin diseases. Here, we aimed to investigate the regulatory effects of GCs in human skin cells of different epidermal and dermal layers. We found that Dex induced TLR2 expression mainly in undifferentiated and less in calcium-induced differentiated keratinocytes but not in HaCaT cells or fibroblasts, however, Dex reduced TLR1/6 expression. Stimulation with Dex under inflammatory conditions further increased TLR2 but not TLR1 or TLR6 levels in keratinocytes. Increased ligand-induced interaction of TLR2 with MyD88 and expression of the adaptor protein TRAF6 indicated enhanced TLR2 signalling, whereas TLR2/1 or TLR2/6 signalling was not increased in Dex-pretreated keratinocytes. GC-increased TLR2 expression was negatively regulated by JNK MAPK signalling when stimulated with Propionibacterium acnes. Our results provide novel insights into the molecular mechanisms of glucocorticoid-mediated expression and function of TLR2 in human skin cells and the understanding of the mechanisms of corticosteroid side effects.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Skin
/
Dexamethasone
/
Gene Expression Regulation
/
MAP Kinase Signaling System
/
Toll-Like Receptor 2
/
Glucocorticoids
/
Anti-Inflammatory Agents
Language:
En
Journal:
J Steroid Biochem Mol Biol
Journal subject:
BIOLOGIA MOLECULAR
/
BIOQUIMICA
Year:
2017
Document type:
Article
Affiliation country:
Germany