Glinka Danielle M, MacGregor Gordon G
Alabama College of Osteopathic Medicine, Dothan, Alabama, USA.
Orlando College of Osteopathic Medicine, Winter Garden, Florida, USA.
JID Innov. 2025 Apr 3;5(4):100369. doi: 10.1016/j.xjidi.2025.100369. eCollection 2025 Jul.
Atopic dermatitis (AD) is a chronic inflammatory skin condition with evidence of defects in the barrier properties of the epidermis. Changes in the permeability properties of the tight junction have been reported in AD, and reversing this leaky tight junction may be a potential treatment for AD. This study aimed to determine the effect of larazotide, an antagonist of the protease-activated receptor 2, on the permeability and barrier properties of the tight junctions in keratinocyte monolayers. Normal human epithelial keratinocytes were grown in culture on permeable supports. The effects of larazotide on transepithelial resistance and permeability properties of keratinocyte monolayers were studied before and after histamine challenge. Larazotide mitigated the disruptive effect of histamine on epithelial permeability by increasing the electrical resistance and decreasing epithelial permeability. Larazotide may be beneficial as a topical therapeutic for AD; however, the permeability properties of the short-peptide larazotide through the uppers layers of the epidermis is currently unknown. In conclusion, the protease-activated receptor 2 antagonist larazotide has a protective effect on keratinocyte monolayers and may be useful as an adjunct therapeutic agent to enhance barrier function and promote epidermal healing in AD.
特应性皮炎（AD）是一种慢性炎症性皮肤病，有证据表明表皮屏障特性存在缺陷。AD中已报道紧密连接的通透性发生变化，逆转这种渗漏的紧密连接可能是AD的一种潜在治疗方法。本研究旨在确定蛋白酶激活受体2拮抗剂拉佐替丁对角质形成细胞单层中紧密连接的通透性和屏障特性的影响。正常人上皮角质形成细胞在可渗透支持物上培养。在组胺激发前后研究了拉佐替丁对角质形成细胞单层跨上皮电阻和通透性的影响。拉佐替丁通过增加电阻和降低上皮通透性减轻了组胺对上皮通透性的破坏作用。拉佐替丁作为AD的局部治疗药物可能有益；然而，短肽拉佐替丁通过表皮上层的通透性目前尚不清楚。总之，蛋白酶激活受体2拮抗剂拉佐替丁对角质形成细胞单层有保护作用，可能作为辅助治疗剂增强屏障功能并促进AD中的表皮愈合。
