Immunopharmacology, Field of Biofunctional Control, Medical Information Science Division, United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, Japan.
J Pharmacol Sci. 2012;118(2):266-74. doi: 10.1254/jphs.11193fp. Epub 2012 Feb 3.
Formaldehyde (FA) is irritating to the skin and is the main cause of sick building syndrome. However, the cutaneous reaction induced by long-term FA exposure has not been fully investigated. In our previous study, we demonstrated that repeated painting of 2% - 10% FA on mouse ears caused marked ear swelling and increased mRNA expression of transient receptor potential vanilloid 1 (TRPV1) and neurotrophins in the ear. TRPV1 is reported to be involved in neurogenic inflammation; therefore, in the present study, we investigated the role of TRPV1 in FA-induced skin inflammation using TRPV1 gene-knockout mice. Mice were painted with 5% FA once a week for 5 weeks, and ear swelling and mRNA expression were investigated. Ear swelling and increased expression of neurotrophins mRNA by FA provocation in wild-type mice were attenuated by disruption of the TRPV1 gene. Furthermore, painting with a threshold dose of capsaicin, which does not induce ear swelling in intact mice, caused marked ear swelling after painting the ear 5 times with FA, indicating that inflamed tissues after FA application are hypersensitive to various ligands of TRPV1 in mice. These results demonstrated that neurogenic inflammation via TRPV1 and neurotrophins could be involved in FA-induced dermatitis.
甲醛(FA)会刺激皮肤,是导致病态建筑综合征的主要原因。然而,长期暴露于 FA 所引起的皮肤反应尚未被充分研究。在我们之前的研究中,我们证明了在小鼠耳朵上重复涂抹 2%-10%FA 会导致明显的耳肿胀,并增加耳朵中瞬时受体电位香草酸 1(TRPV1)和神经营养因子的 mRNA 表达。TRPV1 被报道与神经原性炎症有关;因此,在本研究中,我们使用 TRPV1 基因敲除小鼠研究了 TRPV1 在 FA 诱导的皮肤炎症中的作用。每周一次给小鼠涂抹 5%FA,共 5 周,然后检测耳肿胀和 mRNA 表达情况。在野生型小鼠中,FA 诱发的耳肿胀和神经营养因子 mRNA 表达增加,通过 TRPV1 基因缺失得到了减弱。此外,用辣椒素(capsaicin)进行阈值剂量的涂抹,不会引起完整小鼠的耳肿胀,而在 FA 涂抹 5 次后,会引起明显的耳肿胀,表明 FA 应用后的发炎组织在小鼠中对 TRPV1 的各种配体变得敏感。这些结果表明,通过 TRPV1 和神经营养因子的神经原性炎症可能参与了 FA 诱导的皮炎。