XXXX donors suppress chemokine production by keratinocytes in vitro and in vivo.

@entity1 @entity5737 @entity12557 @entity39 @entity5750 @entity40803 @entity687 @entity2842 @entity12558 @entity842 @entity6897 @entity2071 @entity371
@entity842 (NO) is involved in the modulation of inflammatory responses. In psoriatic skin, NO is highly produced by epidermal keratinocytes in response to interferon-gamma and tumor @entity39 factor-alpha. In this study, we investigated whether the NO donors, @entity12557 ( @entity12558 ) and @entity40803 , could regulate chemokine production by @entity1 keratinocytes activated with interferon-gamma and tumor @entity39 factor-alpha. In addition, we studied the effects of the topical application of a @entity12558 ointment on chemokine expression in lesional psoriatic skin. NO donors diminished in a dose-dependent manner and at both mRNA and protein levels the @entity371 , @entity5737 , and @entity2842 expression in keratinocytes cultured from healthy @entity1 and psoriatic @entity1 . In contrast, constitutive and induced @entity687 production was unchanged. @entity12558 -treated psoriatic skin showed reduction of @entity371 , @entity5737 , and @entity2842 , but not @entity687 expression by keratinocytes. Moreover, the number of @entity5750 (+) and CD3(+) cells infiltrating the epidermis and papillary dermis diminished significantly. NO donors also down-regulated @entity2071 protein expression without affecting mRNA accumulation in vitro, and suppressed keratinocyte @entity2071 in vivo. Finally, NO donors inhibited nuclear factor-kappa B and @entity6897 , but not AP-1 activities in transiently transfected keratinocytes. These results define NO donors as negative regulators of chemokine production by keratinocytes.
