Curcumol reprograms the psoriatic microenvironment by interrupting the IL-36-NLR...

연구 요약

Curcumol reprograms the psoriatic microenvironment by interrupting the IL-36-NLRP3-NETs inflammatory circuit.

Biochemical and biophysical research communications 학술지에 발표된 이 연구는 Quan SL, Zhang ZH, An YM 외 연구팀이 수행하였습니다.

이 연구는 'Curcumol reprograms the psoriatic microenvironment by interrupting the IL-36-NLRP3-NETs inflammatory circuit.'에 대한 과학적 분석을 제공합니다.

핵심 내용

Psoriasis, a chronic immune-mediated dermatosis, poses significant therapeutic challenges due to its complex multifactorial pathogenesis. Curcumol, a bioactive sesquiterpenoid derived from Rhizoma Curcumae, demonstrates broad-spectrum pharmacological activities including notable anti-inflammatory and immunomodulatory properties. We first demonstrated that curcumol disrupts the synergistic pro-inflammatory crosstalk between fibroblasts and keratinocytes by suppressing Poly(I:C)/LPS-induced expression of IL-36α, IL-36γ, and NLRP3 inflammasome activation. Using an ex vivo model, we further showed that curcumol interrupts a self-amplifying loop between IL-36γ and the NLRP3 inflammasome. In imiquimod-induced murine psoriasis, curcumol not only ameliorated skin inflammation and restored keratinocyte differentiation but also profoundly reshaped the immune landscape by dual targeting of inflammasome activation and neutrophil NETosis, thereby attenuating the infiltration of neutrophils and macrophages. These findings reveal that curcumol alleviates psoriatic pathology via coordinated modulation of the IL-36γ-NLRP3-NETs inflammatory circuit, highlighting its potential as a novel multi-target therapeutic strategy for psoriasis management.

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