Skin Barrier Recovery by Protease-Activated Receptor-2 Antagonist Lobaric Acid
| Autor: | Jong Il Park, Ji Eun Lee, Hyunjin Chung, Yeon Ah Joo, Cheol Hwan Myung, Jae Sung Hwang, So-Hyun Yoon |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
MAPK/ERK pathway Chemokine Biochemistry 03 medical and health sciences Drug Discovery Receptor Involucrin Protease-activated receptor 2 Atopic dermatitis Pharmacology integumentary system biology Chemistry Lobaric acid PAR2 Molecular biology Skin barrier Hairless HaCaT 030104 developmental biology biology.protein Molecular Medicine Original Article Tumor necrosis factor alpha |
| Zdroj: | Biomolecules & Therapeutics |
| ISSN: | 1976-9148 2005-4483 |
| DOI: | 10.4062/biomolther.2016.011 |
| Popis: | Atopic dermatitis (AD) results from gene and environment interactions that lead to a range of immunological abnormalities and breakdown of the skin barrier. Protease-activated receptor 2 (PAR2) belongs to a family of G-protein coupled receptors and is expressed in suprabasal layers of the epidermis. PAR2 is activated by both trypsin and a specific agonist peptide, SLIGKV-NH₂ and is involved in both epidermal permeability barrier homeostasis and epithelial inflammation. In this study, we investigated the effect of lobaric acid on inflammation, keratinocyte differentiation, and recovery of the skin barrier in hairless mice. Lobaric acid blocked trypsin-induced and SLIGKV-NH2-induced PAR2 activation resulting in decreased mobilization of intracellular Ca²⁺ in HaCaT keratinocytes. Lobaric acid reduced expression of interleukin-8 induced by SLIGKV-NH₂ and thymus and activation regulated chemokine (TARC) induced by tumor necrosis factor-a (TNF-α) and IFN-γ in HaCaT keratinocytes. Lobaric acid also blocked SLIGKV-NH₂-induced activation of ERK, which is a downstream signal of PAR2 in normal human keratinocytes (NHEKs). Treatment with SLIGKV-NH₂ downregulated expression of involucrin, a differentiation marker protein in HaCaT keratinocytes, and upregulated expression of involucrin, transglutamase1 and filaggrin in NHEKs. However, lobaric acid antagonized the effect of SLIGKV-NH₂ in HaCaT keratinocytes and NHEKs. Topical application of lobaric acid accelerated barrier recovery kinetics in a SKH-1 hairless mouse model. These results suggested that lobaric acid is a PAR2 antagonist and could be a possible therapeutic agent for atopic dermatitis. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|