Glucocorticoids promote CCL20 expression in keratinocytes

Area of Science:

• Dermatology
• Immunology
• Molecular Biology

Background:

• Glucocorticoids (GCs) are typically immunosuppressive but can worsen skin inflammation in conditions like rosacea.
• GCs promote CCL20, a pro-inflammatory cytokine, in lung epithelia, contributing to steroid-resistant asthma.
• In skin, CCL20 recruits inflammatory cells and is elevated in papulopustular rosacea.

Purpose of the Study:

• To investigate the effect of GCs on CCL20 expression in human keratinocytes.
• To elucidate the molecular mechanisms underlying GC-induced CCL20 expression.

Main Methods:

• Quantitative reverse transcriptase polymerase chain reaction and ELISA were used to assess CCL20 expression.
• RNA interference and chemical inhibitors were employed for selective pathway inhibition.
• Chromatin immunoprecipitation and reporter assays were used to study GC receptor binding and enhancer activity.

Main Results:

• GC treatment elevated CCL20 expression in human keratinocytes and murine skin, even with TNF-α stimulation.
• GCs repressed inflammatory pathways like NF-κB and p38 MAPK.
• Activated GC receptor directly bound to the CCL20 enhancer, overriding inhibitory effects and promoting CCL20 expression.

Conclusions:

• GCs induce CCL20 expression in keratinocytes through direct binding to the CCL20 enhancer.
• This mechanism may explain increased inflammation in steroid-exacerbated skin diseases.
• Findings reveal a novel pathway for GC action in skin inflammation.