Abstract
Objective
Atopic dermatitis (AD) involves complex immune dysregulation, with the IL-18 BP/IL-18 axis emerging as a critical yet underexplored regulator of pathological inflammation. While α-boswellic acid (α-BA) has shown therapeutic promise in AD, its role in regulating the IL-18 BP/IL-18 axis under the inflammatory microenvironment is unclear. This study aimed to elucidate whether α-BA could restore IL-18 BP/IL-18 homeostasis and thus suppress inflammation while preserving immune defense.
Methods
A two-sample Mendelian randomization (MR) analysis using summary-level genome-wide association data was conducted to evaluate the potential causal contribution of circulating IL-18 levels to AD susceptibility. DNFB-induced AD mouse model and TNF-α/IFN-γ-stimulated HaCaT cells were used to evaluate α-BA’s effects on barrier function, cytokine profiles, and IL-18 BP/IL-18 axis modulation. RNA sequencing (RNA-seq) was employed to identify the critical mediator of α-BA.
Results
MR analysis showed a statistically significant but modest association between genetically predicted circulating IL-18 levels and AD risk (OR=1.003,
P
Conclusions
α-BA may alleviate AD by modulating the IL-18 BP/IL-18 axis and downstream MyD88/NF-κB signaling pathways. MME may contribute to α-BA-mediated regulation of the IL-18 BP/IL-18 axis.