NITRIC OXIDE IN THE SKIN AND UVB INFLUENCE

一氧化氮（NO）是一种参与多种生物学功能的细胞间信使分子，在哺乳动物器官中由NO合酶（NOS）产生。诱导型NOS（iNOS）在各种类型的组织和细胞中由内毒素、干扰素-γ（IFN-γ）、白细胞介素-1（IL-1）和肿瘤坏死因子-α（TNF-α）单独或组合诱导。在这项研究中，我们研究了是否诱导型一氧化氮合酶诱导的表皮中的一些皮肤疾病和在姜黄素刺激的角质形成细胞。当用白细胞介素-1 β和脂多糖刺激时，分离的大鼠表皮细胞在上清液中产生亚硝酸盐。消耗IA阳性细胞的表皮细胞轻微消除亚硝酸盐的生产活动。Western blot检测显示，在150 kDa处有一条主带。同样的蛋白质带也可见于人角质形成细胞系HSC-1，与相同的刺激剂培养。用iNOS特异性单克隆抗体染色时， ...更多信息 用抗生物素蛋白-生物素-过氧化物酶免疫组化法检测抗人源性抗体，结果表明，苔藓样组织反应、银屑病、胶原病和特应性皮炎等皮肤病的表皮对抗人源性抗体呈阳性反应。在银屑病和特应性皮炎中，局部使用类固醇药物可降低表达，并随疾病活动度的改善而改善。过敏型与巴豆刺激型接触性皮炎皮损表皮iNOS表达无明显差异。与正常人相比，特应性皮炎患者外周血细胞具有刺激角质形成细胞产生NO的能力。本实验观察了UVB照射后角朊细胞产生亚硝酸盐的能力以及NOS抑制剂对UVB照射后耳肿胀和晒伤细胞形成的影响。在白细胞介素1（IL-1）刺激的转化角质形成细胞系的上清液中鉴定出亚硝酸盐。5 mJ/cm^2的UVB使亚硝酸盐的产生增加。亚硝酸盐不产生的角质形成细胞照射，但没有刺激与IL-1。BALB/c小鼠经200 mJ/cm ^2 UVB照射后24小时，耳肿胀，有晒伤细胞。在照射前给小鼠注射NOS抑制剂N^G-硝基-L-精氨酸甲酯（L-NAME），可显著抑制小鼠耳肿胀，并抑制晒伤细胞的形成。这些发现表明，NO产生的皮肤中的UVB照射有助于角质形成细胞损伤以及急性皮肤反应，如UVB水肿。少

Nitric oxide (NO) is an intercellular messenger molecule involved in a variety of biological functions and is generated in mammalian organs by NO synthase (NOS). Inducidle NOS (iNOS) is induced in various types of tissues and cells by endotoxins, interferon-gamma (IFN-gamma), interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha), alone or in combination. In this study, we examined whether iNOS is induced in the epidermis of some skin diseases and in cytokine-stimulated keratinocytes. Isolated rat epidermal cells produced nitrite in the supernatant fluid when stimulated with interleukin-1beta and lipopolysaccharide. Depletion of Ia-positive cells from the epidermal cells slightly eliminated the activity of nitrite production. Homogenates of the stimulated cells exhibited a main band at 150kDa by the Western blot method. The same protein bands were also visible in the human keratinocyte cell line, HSC-1, cultured with the same stimulants. When stained with iNOS-specific monocl … More onal antibodies by the avidin-biotin-peroxidase immuno-histochemical method, the epidermis of some skin diseases, including lichenoid tissue reactions, psoriasis, collagen diseases and atopic dermatitis, showed a positive reaction to the antibodies. Topical medication of steroids decreased the expression with improvement of the disease activity in psoriasis and atopic dermatitis. There was no diffrence in iNOS expression in the epidermis between allergic type and croton-induced irritant type contact dermatitis. Peripheral blood cells had an ablity to stimulate keratinocytes to produce NO in atopic dermatitis patients compared to normal volunteers. These findings suggest that iNOS probably induced in keratincytes by cytokines is relevant to the pathology of some inflammatory skin diseases.The nitrite production by UVB-irradiated kerationocytes and the effects of the NOS inhibitor on ear swelling and sunburn cell formation after UVB irradiation were examined. Nitrite was identified in the supernatant fluid of interleukin 1 (IL-1) -stimulated transformed keratinocyte cell lines. Five mJ/cm^2 UVB augumented the production of nitrite. Nitrite was not generated in the keratinocytes irradiated but not stimulated with IL-1. When BALB/c mice were irradiated with 200mJ/cm^2 UVB,ear swelling and sunburn cells were observed 24 hours after irradiation. When the mice were injected with a NOS inhibitor, N^G-nitro-L-arginine methyl ester (L-NAME), before irradiation, ear swelling was significantly suppressed.Furthermore, such injection also suppressed the formation of sunburn cells. These findings suggest that NO produced in the skin by UVB irradiation contributes to keratinocyte injury as well as acute dermal reactions such as UVB edema. Less