Howell Michael D, Kim Byung Eui, Gao Peisong, Grant Audrey V, Boguniewicz Mark, Debenedetto Anna, Schneider Lynda, Beck Lisa A, Barnes Kathleen C, Leung Donald Y M
Department of Pediatrics, National Jewish Medical and Research Center, Denver, CO 80206, USA.
J Allergy Clin Immunol. 2007 Jul;120(1):150-5. doi: 10.1016/j.jaci.2007.04.031. Epub 2007 May 23.
Atopic dermatitis (AD) is a chronic inflammatory skin disease that is characterized by a defective skin barrier function. Recent studies have reported mutations of the skin barrier gene encoding filaggrin in a subset of patients with AD.
We investigated whether reduced filaggrin expression was found in patients with AD who were not carriers of known filaggrin mutations and whether filaggrin expression was modulated by the atopic inflammatory response.
Filaggrin expression was measured in skin biopsies and cultured keratinocytes using real-time RT-PCR and immunohistochemistry. Filaggrin loss-of-function mutations were screened in a total of 69 subjects.
Compared with normal skin, filaggrin expression was significantly reduced (P < .05) in acute AD skin, with further reduction seen in acute lesions from 3 European American subjects with AD who were heterozygous for the 2282del4 mutation. This was confirmed by using immunohistochemistry. AD skin is characterized by the overexpression of IL-4 and IL-13. Keratinocytes differentiated in the presence of IL-4 and IL-13 exhibited significantly reduced filaggrin gene expression (0.04 +/- 0.01 ng filaggrin/ng glyceraldehyde 3-phosphate dehydrogenase; P < .05) compared with media alone (0.16 +/- 0.03).
Patients with AD have an acquired defect in filaggrin expression that can be modulated by the atopic inflammatory response.
The atopic immune response contributes to the skin barrier defect in AD; therefore, neutralization of IL-4 and IL-13 could improve skin barrier integrity.
特应性皮炎（AD）是一种慢性炎症性皮肤病，其特征为皮肤屏障功能缺陷。最近的研究报道，在一部分AD患者中存在编码丝聚合蛋白的皮肤屏障基因突变。
我们研究了在非已知丝聚合蛋白突变携带者的AD患者中是否发现丝聚合蛋白表达降低，以及丝聚合蛋白表达是否受特应性炎症反应调节。
使用实时逆转录聚合酶链反应（RT-PCR）和免疫组织化学法检测皮肤活检组织和培养的角质形成细胞中的丝聚合蛋白表达。对总共69名受试者进行丝聚合蛋白功能丧失突变筛查。
与正常皮肤相比，急性AD皮肤中的丝聚合蛋白表达显著降低（P <.05），在3名携带2282del4突变杂合子的欧美AD患者的急性皮损中丝聚合蛋白表达进一步降低。这通过免疫组织化学得到证实。AD皮肤的特征是白细胞介素-4（IL-4）和白细胞介素-13（IL-13）过表达。与单独培养基（0.16 +/- 0.03）相比，在IL-4和IL-13存在下分化的角质形成细胞显示丝聚合蛋白基因表达显著降低（0.04 +/- 0.01 ng丝聚合蛋白/ng甘油醛-3-磷酸脱氢酶；P <.05）。
AD患者存在后天性丝聚合蛋白表达缺陷，该缺陷可受特应性炎症反应调节。
特应性免疫反应导致AD中的皮肤屏障缺陷；因此，中和IL-4和IL-13可改善皮肤屏障完整性。
