Tenaud Isabelle, Khammari Amir, Dreno Brigitte
Department of Dermatology, CHU, Nantes, France.
Exp Dermatol. 2007 Jun;16(6):500-6. doi: 10.1111/j.1600-0625.2007.00552.x.
The anti-inflammatory mechanisms of adapalene, a synthetic retinoid used for the treatment of acne patients, are partially understood. They seem particularly related to the modulation of the non-specific immunity. Recent studies have shown that Toll-like receptor (TLR)-2 expression, a receptor of the innate immune system, was increased in acne lesions and could play an essential role in acne-linked inflammation. The aim of our study was to investigate the new mechanisms of the anti-inflammatory activity of adapalene in vitro, and more specifically the modulatory effect of adapalene on the expression of TLR-2, CD1d, a cell surface glycoprotein that plays a role as antigen-presenting molecules and is responsible for the development of cutaneous inflammation, and also on the expression and the secretion of the anti-inflammatory interleukin (IL)-10 cytokine. Both explants of normal human skin and explants of acne patients were incubated with adapalene (10(-7) or 10(-6) M) or the control medium for 24 h. Evaluation of epidermal expression by immunohistochemistry showed a decreased expression of TLR-2 and IL-10 in explants of normal skin and explants of acne with adapalene. On the contrary, adapalene increased CD1d expression in explants of acne patients. Thus, adapalene can modulate the epidermal immune system by increasing the CD1d expression and by decreasing the IL-10 expression by keratinocytes. Moreover, these modulations could increase the interactions between dendritic cells and T lymphocytes and could strengthen the antimicrobial activity against Propionibacterium acnes. The decreased expression of TLR-2 by the keratinocytes can contribute to explain the anti-inflammatory activity of adapalene observed in clinical practice.
阿达帕林是一种用于治疗痤疮患者的合成维甲酸，其抗炎机制已部分为人所知。它们似乎与非特异性免疫的调节特别相关。最近的研究表明，Toll样受体（TLR）-2的表达，一种先天免疫系统的受体，在痤疮皮损中增加，并且可能在痤疮相关炎症中起重要作用。我们研究的目的是在体外研究阿达帕林抗炎活性的新机制，更具体地说是研究阿达帕林对TLR-2、CD1d表达的调节作用，CD1d是一种细胞表面糖蛋白，作为抗原呈递分子发挥作用并负责皮肤炎症的发展，以及对抗炎白细胞介素（IL）-10细胞因子表达和分泌的调节作用。将正常人皮肤外植体和痤疮患者的外植体与阿达帕林（10^(-7)或10^(-6) M）或对照培养基孵育24小时。通过免疫组织化学评估表皮表达显示，在使用阿达帕林的正常皮肤外植体和痤疮外植体中，TLR-2和IL-10的表达降低。相反，阿达帕林增加了痤疮患者外植体中CD1d的表达。因此，阿达帕林可以通过增加CD1d表达和降低角质形成细胞的IL-10表达来调节表皮免疫系统。此外，这些调节可以增加树突状细胞和T淋巴细胞之间的相互作用，并可以增强对痤疮丙酸杆菌的抗菌活性。角质形成细胞中TLR-2表达的降低有助于解释在临床实践中观察到的阿达帕林的抗炎活性。
