Narrowband ultraviolet B inhibits innate cytosolic double-stranded RNA receptors in psoriatic skin and keratinocytes
Type:Uv phototherapy Time:2014-12-12 15:21:47Narrowband ultraviolet B inhibits innate cytosolic double-stranded RNA receptors in psoriatic skin and keratinocytes.
R¨¢cz E1, Prens EP, Kant M, Florencia E, Jaspers NG, Laman JD, de Ridder D, van der Fits L.
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Abstract
BACKGROUND:
The mode of action of narrowband ultraviolet B (NB-UVB) therapy in clearing psoriasis is incompletely understood, and in vivo
studies at the molecular level in patients undergoing NB-UVB therapy are limited. We previously demonstrated increased
expression and activity of double-stranded RNA (dsRNA) receptors in psoriasis lesions, and suggested that this enhanced
innate signalling contributed to the maintenance of psoriatic inflammation.
OBJECTIVES:
We investigated whether NB-UVB affects dsRNA receptor expression and function in vivo as well as in vitro.
METHODS:
Skin samples of patients with psoriasis undergoing NB-UVB treatment were analysed for epidermal messenger RNA (mRNA)
expression of the various dsRNA receptors by microarray and quantitative reverse transcription-polymerase chain reaction.
Primary human keratinocytes were irradiated with NB-UVB and stimulated with interferon (IFN)-¦Á or IFN-¦Ã, critical cytokines
in psoriasis. The dsRNA analogue polyriboinosinic-polyribocytidylic acid was used to assess the functional responsiveness of
the cells to dsRNA.
RESULTS:
NB-UVB therapy of patients with psoriasis resulted in a significantly reduced mRNA expression of the activating dsRNA
receptors MDA5 (IFIH1) and RIG-I (DDX58). On the other hand, expression of LGP2 (DHX58), toll-like receptor 3 (TLR3) and PKR
(EIF2AK2) was not affected. In vitro, NB-UVB irradiation completely blocked the upregulation of four of the dsRNA receptors
in primary human keratinocytes stimulated with IFN-¦Á or IFN-¦Ã, resulting in an attenuated inflammatory response to dsRNA.
CONCLUSIONS:
Our results show that NB-UVB irradiation inhibits the local innate inflammatory response to dsRNA, and suggest a novel
mechanism of action of NB-UVB phototherapy in psoriasis.
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