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


CONCLUSIONS
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.
Leng
Hong
H
Department of Dermatology, Hua-Shan Hospital, Fudan University, Shanghai, China.
Luo
Xiaoqun
X
Ma
Li
L
Kang
Kefei
K
Zheng
Zhizhong
Z
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004139:Dinitrofluorobenzene / Q000008:administration & dosage; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors*; D005260:Female; D007108:Immune Tolerance / Q000528:radiation effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D014466:Ultraviolet Rays
D047428:Protein Kinase Inhibitors; D004139:Dinitrofluorobenzene; D048049:Extracellular Signal-Regulated MAP Kinases