本研究评估了克瑞沙莫罗联合维生素D治疗过敏性接触性皮炎的疗效和潜在机制。在克里斯塔波罗的时候,磷酸二酯酶4抑制剂,和维生素D类似物通常用于治疗特应性皮炎,它们在过敏性接触性皮炎(ACD)中的联合治疗潜力仍有待探索.鉴于它们的抗炎特性,我们假设,在缓解过敏性接触性皮炎的症状和潜在机制方面,联合使用crisaborole和维生素D可提供更优越的疗效.体外,用肿瘤坏死因子-α和干扰素-γ刺激的HaCaT细胞用crisaborole和维生素D联合治疗,然后进行细胞因子表达分析。在体内,将雄性C57BL/6小鼠分为5组,并进行相应的治疗:空白对照,二硝基氯苯诱导模型,只有克里斯塔波罗,单独的维生素D,在第14天,测量背部皮肤和耳朵厚度,其次是全面的病理评估。体内和体外实验显示,DNCB+VD+Cri组炎症因子的表达程度明显低于DNCB组。组织学分析显示,与DNCB组相比,联合治疗组明显减轻表皮角化过度,改善表皮透皮失水,皮炎评分降低,肥大细胞浸润减少.此外,它降低了IL-6,IL-4,TNF-α的表达水平,iNOS,IL-17,CC趋化因子配体2(CCL2),和CC趋化因子受体2(CCR2)。CCL2识别CCR2并刺激炎症细胞,增强炎症反应。CCL2表达增加与ACD中炎症和树突状细胞浸润增强相关,而CCL2的下调减弱炎症。因此,在ACD小鼠模型中,联合使用crisaborole和维生素D显示优于单一疗法的治疗效果.在过敏性接触性皮炎的小鼠模型中,维生素D和crisabororole的组合显着减少了炎症和表皮角化过度,与任一单独治疗相比,表现出优异的治疗效果。这表明联合疗法可能是预防和治疗过敏性接触性皮炎的有希望的方法。
This study evaluated the therapeutic efficacy and underlying mechanisms of crisaborole combined with vitamin D in the treatment of allergic contact dermatitis. While crisaborole, a phosphodiesterase 4 inhibitor, and vitamin D analogs are commonly used in the treatment of atopic dermatitis, their combined therapeutic potential in allergic contact dermatitis (ACD) remains unexplored. Given their anti-inflammatory properties, we hypothesized that the combination of crisaborole and vitamin D could offer superior efficacy in mitigating the symptoms and underlying mechanisms of allergic contact dermatitis. In vitro, HaCaT cells stimulated with tumor necrosis factor-α and interferon-γ were treated with a combination of crisaborole and vitamin D, followed by cytokine expression analysis. In vivo, male C57BL/6 mice were divided into five groups and treated accordingly: blank control, dinitrochlorobenzene-induced model, crisaborole alone, vitamin D alone, and a combination of crisaborole and vitamin D. On day 14, dorsal skin and ear thickness were measured, followed by comprehensive pathological evaluations. In vivo and in vitro experiments showed that the expression levels of inflammatory factors were significantly lower in the DNCB + VD + Cri group than in the DNCB group. Histological analyses revealed that, compared with the DNCB group, the combined treatment group significantly reduced epidermal hyperkeratosis, improved epidermal transdermal water loss, decreased dermatitis scores, and diminished mast cell infiltration. Moreover, it lowered the expression levels of IL-6, IL-4, TNF-α, iNOS, IL-17, CC chemokine ligand 2 (CCL2), and CC chemokine receptor 2 (CCR2). CCL2 recognizes CCR2 and stimulates inflammatory cells, enhancing the inflammatory response. Increased CCL2 expression correlates with heightened inflammation and dendritic cell infiltration in ACD, while downregulation of CCL2 attenuates inflammation. Thus, the combined use of crisaborole and vitamin D demonstrates superior therapeutic efficacy over monotherapy in a mouse model of ACD. The combination of vitamin D and crisaborole significantly reduces inflammation and epidermal hyperkeratosis in a mouse model of allergic contact dermatitis, demonstrating superior therapeutic efficacy compared to either treatment alone. This suggests that the combined therapy could be a promising approach for the prevention and treatment of allergic contact dermatitis.