Inhibition of T helper 2 chemokine production by narrowband ultraviolet B in cultured keratinocytes

Inhibition of T helper 2 chemokine production by narrowband ultraviolet B in cultured keratinocytes
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DOI:
10.1111/j.1365-2133.2007.07774.x
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发表时间:
2007-05-01
影响因子:
10.3
通讯作者:
Tokura, Y.
Tokura, Y.
中科院分区:
医学1区
文献类型:
--
作者:
Hino, R.;Kobayashi, M.;Tokura, Y.

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背景窄带紫外线B(NB-UVB)近来已被用于治疗各种皮肤病。其对角质形成细胞产生细胞因子和趋化因子的影响尚不清楚。目的与宽带(BB)-UVB相比,探讨NB-UVB对角质形成细胞产生趋化因子和促炎细胞因子的影响。方法正常人表皮角质形成细胞(或在一些实验中的人角质形成细胞系HaCaT)以10,100,500或1000 mJ cm(-2)或10或100 mJ cm(-2)的BB-UVB。在存在或不存在200 U mL(-1)干扰素(IFN)-γ的情况下维持培养物。通过酶联免疫吸附试验分析72 h培养上清液,以定量T辅助细胞(Th)1趋化因子(IFN诱导蛋白10和IFN-γ诱导的单核因子)、Th 2趋化因子[巨噬细胞衍生趋化因子(MDC)和胸腺活化调节趋化因子(TARC)]和促炎细胞因子[白细胞介素(IL)-1 α和肿瘤坏死因子(TNF)-α]。这些分子的mRNA的表达,同时进行了评估,通过逆转录酶-聚合酶链反应。还测试了培养物上清液对Th 1和Th 2细胞的趋化活性。结果NB-UVB和BB-UVB均能促进IL-1 α和TNF-α的产生,但NB-UVB的促进作用不及BB-UVB。两种波长范围的UVB增强或没有影响Th 1趋化因子的产生,但抑制Th 2趋化因子MDC和TARC的产生。这是证实了趋化实验,这表明减少趋化活性的Th 2细胞的培养上清NB-UVB照射角质形成cells.Conclusions NB-UVB减少产生的Th 2趋化因子,而不产生过量的促炎细胞因子,这表明其对Th 2介导的皮肤疾病的治疗效果,以及其在临床使用中的相对安全性。
Background Narrowband ultraviolet B (NB-UVB) has recently been used for the treatment of various skin disorders. Its effects on the production of cytokines and chemokines by keratinocytes are unknown.Objectives To investigate the effect of NB-UVB on production of chemokines and proinflammatory cytokines by keratinocytes in comparison with broadband (BB)-UVB.Methods Normal human epidermal keratinocytes (or the human keratinocyte cell line HaCaT in some experiments) at semiconfluency were irradiated with NB-UVB at 10, 100, 500 or 1000 mJ cm(-2) or BB-UVB at 10 or 100 mJ cm(-2). The cultures were maintained in the presence or absence of interferon (IFN)-gamma at 200 U mL(-1). The 72-h culture supernatants were analysed by enzyme-linked immunosorbent assay to quantify T helper (Th)1 chemokines (IFN-inducible protein 10 and monokine induced by IFN-gamma), Th2 chemokines [macrophage-derived chemokine (MDC) and thymus and activation-regulated chemokine (TARC)] and proinflammatory cytokines [interleukin (IL)-1 alpha and tumour necrosis factor (TNF)-alpha]. The expression of mRNA for these molecules was simultaneously assessed by reverse transcriptase-polymerase chain reaction. The culture supernatants were also tested for their chemotactic activity for Th1 and Th2 cells. The two UVB sources were compared on the basis of their minimal erythemal doses and clinically used doses.Results Although both NB-UVB and BB-UVB increased the production of IL-1 alpha and TNF-alpha, the augmentative effect of NB-UVB was less than that of BB-UVB. Both wavelength ranges of UVB enhanced or had no effect on Th1 chemokine production, but suppressed the production of Th2 chemokines MDC and TARC. This was confirmed by chemotactic assay, which showed decreased chemotactic activity for Th2 cells by the culture supernatants from NB-UVB-irradiated keratinocytes.Conclusions NB-UVB reduces the production of Th2 chemokines without excess production of proinflammatory cytokines, suggesting its therapeutic effectiveness on Th2-mediated skin disorders as well as its relative safety in clinical usage.