Skin sensitization, often caused by chemicals like nickel sulfate (NiSO₄), can lead to allergic contact dermatitis (ACD)—a condition marked by inflammation and immune activation. Conventional treatments like corticosteroids are effective but come with side effects such as skin thinning and immune suppression, creating the need for safer alternatives. Pseudopterosins (PsA–D), marine-derived glycosides from the coral Antillogorgia elisabethae, are known for their anti-inflammatory and skin-soothing properties. This study explores PsA–D’s ability to modulate skin immune responses, specifically targeting dendritic cell activation and inflammatory signaling.
Methods
The study utilized isolated dermal dendritic cell (DDC) surrogates and a full-thickness engineered human skin model incorporating DDCs. Both models were treated with PsA–D or dexamethasone prior to NiSO₄ exposure. Researchers evaluated surface activation markers (CD54, CD86), NF-κB pathway activity (via IκBα degradation), pro-inflammatory cytokines (IL-8, IL-6, IL-1β), and mediators like COX-2 and NLRP3 at protein and mRNA levels.
Key Findings
- Dendritic Cell Activation Markers: PsA–D significantly downregulated CD54 and CD86 expression in both models (~1.2–1.7 fold), showing comparable efficacy to dexamethasone.
- NF-κB Pathway Inhibition: PsA–D inhibited IκBα degradation, indicating suppression of NF-κB activation—more selectively than dexamethasone.
- Pro-inflammatory Cytokines: IL-8 (~9.2-fold), IL-6 (~6.7-fold), and IL-1β (fully suppressed) were significantly reduced in DDCs. These effects were mirrored in the skin model at the mRNA level.
- Inflammatory Mediators: COX-2 (~3.5-fold) and NLRP3 (~2.1-fold) mRNA expressions were downregulated in the skin model.
- Comparable to Corticosteroids: Across all parameters, PsA–D’s performance was similar to that of dexamethasone, reinforcing its therapeutic promise.
This study is the first to systematically show that PsA–D reduces skin inflammation by inhibiting dendritic cell activation and suppressing key inflammatory pathways like NF-κB. Its topical potential is strengthened by high skin retention and low systemic absorption due to its lipophilicity. PsA–D presents a compelling natural alternative to corticosteroids for managing skin sensitization and ACD. Future research should focus on enhancing its formulation and evaluating long-term effects to support broader clinical application.
Link to the study: https://www.mdpi.com/1660-3397/23/6/245
