Kim Ji Young, Kim Yoon Jee, Lim Beom Jin, Sohn Hyo Jung, Shin Dongyun, Oh Sang Ho
Department of Dermatology, Cutaneous Biology Research Institute, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
Department of Pathology, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.
Yonsei Med J. 2014 Nov;55(6):1648-55. doi: 10.3349/ymj.2014.55.6.1648.
Recent findings of increased cathelicidin protein and its proteolytic fragments in rosacea suggest a pathogenic role for cathelicidin in this disease. The relationship between cathelicidin and protease-activated receptor 2 (PAR-2) is therefore of interest, as PAR-2, expressed principally in keratinocytes, regulates pro-inflammatory cytokine expression in the skin. The purpose of this study was to determine the relationship between expression of PAR-2 and cathelicidin in rosacea and to test the effect of direct PAR-2 activation on cathelicidin expression in keratinocytes.
Samples from 40 patients with clinicopathologic diagnosis of rosacea and facial skin tissue samples from 20 patients with no specific findings or milium without inflammation were retrieved. Intensities of immunohistochemical staining for PAR-2 and cathelicidin were compared between normal and rosacea-affected skin tissues. Additionally, correlations between PAR-2 and cathelicidin staining intensities within rosacea patients were analyzed. In cultured keratinocytes, changes in PAR-2, cathelicidin, and vascular endothelial growth factor (VEGF) mRNA and protein were analyzed after treatment with PAR-2 activating peptide (AP).
Cathelicidin expression was significantly higher in rosacea skin tissues than in normal tissues (p<0.001), while PAR-2 expression was not significantly higher in rosacea tissues than in normal skin tissues. A positive correlation between PAR-2 and cathelicidin within rosacea samples was observed (R=0.330, p=0.037). After treatment of PAR-2 AP, both mRNA and protein levels for PAR-2, cathelicidin, and VEGF significantly increased in cultured keratinocytes, compared with PAR-2 control peptide treatment.
PAR-2 may participate in the pathogenesis of rosacea through activation of cathelicidin LL-37, a mediator of innate immune responses in the skin.
酒渣鼻患者中cathelicidin蛋白及其蛋白水解片段增加的最新研究结果表明，cathelicidin在该疾病中具有致病作用。因此，cathelicidin与蛋白酶激活受体2（PAR-2）之间的关系备受关注，因为PAR-2主要在角质形成细胞中表达，可调节皮肤中促炎细胞因子的表达。本研究的目的是确定酒渣鼻患者中PAR-2与cathelicidin表达之间的关系，并测试PAR-2直接激活对角质形成细胞中cathelicidin表达的影响。
收集40例经临床病理诊断为酒渣鼻患者的样本以及20例无特定病变或无炎症粟丘疹患者的面部皮肤组织样本。比较正常皮肤组织和酒渣鼻受累皮肤组织中PAR-2和cathelicidin的免疫组化染色强度。此外，分析酒渣鼻患者中PAR-2与cathelicidin染色强度之间的相关性。在培养的角质形成细胞中，用PAR-2激活肽（AP）处理后，分析PAR-2、cathelicidin和血管内皮生长因子（VEGF）的mRNA和蛋白变化。
酒渣鼻皮肤组织中cathelicidin的表达明显高于正常组织（p<0.001），而酒渣鼻组织中PAR-2的表达并不显著高于正常皮肤组织。在酒渣鼻样本中观察到PAR-2与cathelicidin之间呈正相关（R=0.330，p=0.037）。与PAR-2对照肽处理相比，用PAR-2 AP处理后，培养的角质形成细胞中PAR-2、cathelicidin和VEGF的mRNA和蛋白水平均显著增加。
PAR-2可能通过激活cathelicidin LL-37参与酒渣鼻的发病机制，cathelicidin LL-37是皮肤固有免疫反应的介质。
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