Abstract：
:Nitric oxide is an important mediator of excessive cell growth and inflammation associated with many epidermal proliferative disorders. It is a highly reactive oxidant generated in keratinocytes and macrophages via the inducible form of the enzyme nitric oxide synthase (NOS2). In the present studies, we examined the effects of ultraviolet light (UVB, 2.5-25mJ/cm(2)) on interferon-gamma (IFN-gamma)-induced expression of NOS2 in these cells. Transient transfection assays using wild-type and mutant NOS2 promoter/luciferase reporter constructs showed that DNA binding of the transcription factors Stat1 and NF-kappaB was essential for optimal expression of the NOS2 gene. Whereas NF-kappaB was constitutively expressed in both cell types, Stat1 phosphorylation and nuclear binding activity were dependent upon IFN-gamma. UVB light, which is used therapeutically to treat inflammatory dermatosis, was found to suppress IFN-gamma-induced expression of NOS2 mRNA and protein, and nitric oxide production in both keratinocytes and macrophages. In macrophages, this was associated with complete inhibition of NF-kappaB nuclear binding activity and partial (approximately 20-25%) reduction of Stat1 activity. In keratinocytes, both responses were partially reduced at the highest doses of UVB light (15-25mJ/cm(2)). Whereas in macrophages UVB light suppressed NOS2 wild-type promoter-luciferase reporter activity, this activity was stimulated in keratinocytes. These data suggest that UVB light functions to suppress NOS2 gene expression in macrophages by inhibiting the activity of key regulatory transcription factors. In contrast, in keratinocytes, inhibition occurs downstream of NOS2 promoter activity.
journal_name
Biochem Pharmacoljournal_title
Biochemical pharmacologyauthors
Sur R,Heck DE,Mariano TM,Jin Y,Murphy WJ,Laskin JDdoi
10.1016/s0006-2952(02)01419-3subject
Has Abstractpub_date
2002-11-15 00:00:00pages
1469-81issue
10eissn
0006-2952issn
1873-2968pii
S0006295202014193journal_volume
64pub_type
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journal_title：Biochemical pharmacology
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更新日期：2014-05-15 00:00:00
