Department of Dermatology and Venereology, The First Hospital of Jilin University, Changchun, China,
Department of Dermatology and Venereology, The Second Hospital of Jilin University, Changchun, China.
Int Arch Allergy Immunol. 2021;182(2):83-93. doi: 10.1159/000507289. Epub 2020 Dec 7.
Chronic idiopathic urticaria (CIU) represents a common skin disorder often characterized by mast cell activation and secretion of histamine and other proinflammatory factors. E-selectin (SELE) has been implicated in the pathogenesis of common inflammatory cutaneous disorders, while the role of SELE in CIU is yet to be fully understood. Thus, we aimed to investigate the mechanism by which SELE influences CIU in connection with the involvement of mast cells.
SELE expression was measured in blood samples obtained from CIU patients and normal individuals. A CIU mouse model was subsequently established by intradermally injecting a normal saline solution with ovalbumin IgE antiserum into the mice. Loss- and gain-of-function investigations were conducted on the mouse models. The number of degranulated mast cells and the amount of histamine release in vitro were determined. The levels of SELE, tumor necrosis factor (TNF)-α, homologous restriction factor (HRF), and interleukin (IL)-6 levels were determined.
The CIU clinical samples exhibited upregulated SELE, while the CIU mice showed increased mast cell degranulation and an increased rate of histamine directional release, as well as an elevated expression of SELE, TNF-α, HRF, and IL-6. SELE silencing was found to decrease the number of degranulated mast cells and reduce the rate of histamine directional release, along with suppressed TNF-α, HRF, and IL-6 expression, in the serum of CIU mice. Ketotifen was observed to rescue the increased expression of TNF-α, HRF, and IL-6 caused by SELE overexpression.
This study highlights the potential of SELE downregulation to repress inflammatory factor secretion caused by the accumulation of mast cells, which ultimately inhibits the development of CIU.
慢性特发性荨麻疹(CIU)是一种常见的皮肤疾病,其特征通常为肥大细胞激活以及组胺和其他促炎因子的分泌。E-选择素(SELE)已被牵涉到常见炎症性皮肤疾病的发病机制中,而 SELE 在 CIU 中的作用尚未被完全理解。因此,我们旨在研究 SELE 影响 CIU 的机制,同时探讨肥大细胞的参与情况。
测量了从 CIU 患者和正常个体获得的血液样本中的 SELE 表达。随后通过将卵清蛋白 IgE 抗血清的生理盐水溶液皮内注射到小鼠中来建立 CIU 小鼠模型。对小鼠模型进行了缺失和获得功能的研究。体外测定脱颗粒肥大细胞的数量和组胺释放量。测定 SELE、肿瘤坏死因子(TNF)-α、同源限制因子(HRF)和白细胞介素(IL)-6 的水平。
CIU 临床样本表现出上调的 SELE,而 CIU 小鼠显示出肥大细胞脱颗粒增加和组胺定向释放率增加,以及 SELE、TNF-α、HRF 和 IL-6 表达水平升高。沉默 SELE 被发现可减少脱颗粒肥大细胞的数量,并降低组胺定向释放率,同时抑制 CIU 小鼠血清中 TNF-α、HRF 和 IL-6 的表达。酮替芬被观察到可挽救 SELE 过表达引起的 TNF-α、HRF 和 IL-6 表达增加。
本研究强调了下调 SELE 以抑制肥大细胞积累引起的炎症因子分泌的潜力,这最终抑制了 CIU 的发展。