Reversal of ultraviolet B-induced immunosuppression by inhibition of the extracellular signal-regulated mitogen-activated protein kinase
Reversal of ultraviolet B-induced immunosuppression by inhibition of the extracellular signal-regulated mitogen-activated protein kinase
复制标题
通过抑制细胞外信号调节丝裂原激活蛋白激酶逆转紫外线 B 诱导的免疫抑制
DOI：
10.1111/j.1600-0781.2009.00458.x
复制
发表时间：
2009-10-01
影响因子：
2.6
通讯作者：
Zheng, Zhizhong
中科院分区：
文献类型：
--
作者：
Leng, Hong;Luo, Xiaoqun;Zheng, Zhizhong
目的：在体内研究中，提出了细胞外信号调节激酶（ERK）1/2的特异性抑制剂PD 98059（PD）的局部治疗与紫外线B（UVB）暴露相结合，以确认参与UVB诱导的免疫抑制的ERK 1/2的有效性，该免疫抑制可被PD逆转。基于局部UVB诱导的免疫抑制小鼠模型[UVB暴露，然后在耳部位激发前在腹部皮肤上用二硝基氟苯（DNFB）致敏]，在UVB暴露前1小时、暴露前即刻和暴露后6小时，分别测量耳厚度的基线，并在DNFB激发后24 h重新测量以评估耳肿胀反应。结果：与UVB照射组相比，PD照射组小鼠出现明显的接触性过敏反应（P < 0.05），并且与UVB照射组相比，PD照射组小鼠的皮肤组织病理学表现为表皮增厚，淋巴细胞浸润。结论：ERK 1/2丝裂原活化蛋白激酶（MAPK）通路在UVB诱导的局部免疫抑制中起重要作用，其特异性抑制剂PD可阻断ERK 1/2丝裂原活化蛋白激酶（MAPK）通路的功能，对UVB诱导的局部免疫抑制具有保护作用。
Objective: Topical treatment of the specific inhibitor PD98059 (PD) for extracellular signal-regulated kinase (ERK) 1/2 combined with ultraviolet B (UVB) exposure in an in vivo study was proposed to confirm the effectiveness of ERK1/2 involved in UVB-induced immunosuppression that was reversed by PD.Methods: Based on the mouse model of local UVB-induced immunosuppression [UVB exposure, followed by sensitization with dinitrofluorobenzene (DNFB) on the abdomen skin before challenge on the ear site], the PD was applied on the abdomen-irradiated area 1 h, immediately before and 6 It after UVB exposure, respectively. The baseline of ear thickness was measured and remeasured 24 h after the challenge of DNFB for evaluation of ear-swelling response. Histopathologically, the ear biopsies were taken for hematoxylin and eosin staining.Results: Mice that received PD post-irradiation treatment showed a statistically significant contact hypersensitivity compared with the UVB-irradiated mice (P < 0.05), and paralleled with the biopsy showing a thickened epidermis with lymphocyte infiltration. Thus, the PD had abrogated the UV-induced local suppression of contact hypersensitivity.Conclusion: The ERK1/2 mitogen-activated protein kinase (MAPK) pathway plays an important role in the local UVB-induced immunosuppression, and its specific inhibitor PD can arrest its function, resulting in protection against UVB-induced immunosuppression in the present in vivo study.