Inhibition of RIPK1 prevents keratinocyte cell death and reduces skin inflammation in type 1 mediated chronic inflammatory skin diseases - PubMed
a day ago
- #targeted-therapy
- #chronic-inflammatory-skin-diseases
- #RIPK1-inhibition
- Inhibition of RIPK1 prevents keratinocyte cell death and reduces skin inflammation in type 1 mediated chronic inflammatory skin diseases.
- Type 1 mediated chronic inflammatory skin diseases (ISD) include lichen planus (LP) and cutaneous lupus erythematosus (CLE), impacting patients' quality of life.
- RIPK1 is a key regulator of programmed cell death, making it a potential therapeutic target for LP and CLE.
- Markers of apoptosis (Caspase 8) and necroptosis (RIPK3, MLKL) are upregulated in LP and CLE.
- Eclitasertib, a novel RIPK1 inhibitor, restored body temperature in a murine SIRS model and prevented keratinocyte cell death.
- RIPK1 inhibition normalized epidermal architecture and reduced inflammatory cytokines (IL-1α, IL-1β, TNF-α, CCL20) in human epidermis.
- Ex vivo culture of LP and CLE biopsies with Eclitasertib downregulated disease-specific genes and inflammatory pathways.
- Conclusion: RIPK1 inhibition targets epidermal cell death and type 1 mediated skin inflammation in LP and CLE.