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Reversal of ultraviolet B-induced immunosuppression by inhibition of the extracellular signal-regulated mitogen-activated protein kinase

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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 h 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.

Keywords: ERK1/2 MAPK; PD98059; immunosuppression; ultraviolet B

Document Type: Research Article


Affiliations: 1: Department of Dermatology, Hua-Shan Hospital, Fudan University, Shanghai, China, and 2: Case Western Reserve University, Cleveland, OH, USA

Publication date: 2009-10-01

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