Abstract
The mechanisms underlying UVB-induced clearance of psoriasis are incompletely understood.
We compared the cellular and molecular effects of a clinically effective wavelength of UVB
(311nm) with a clinically ineffective wavelength (290nm) in vivo and in vitro to distinguish
bystander effects and utilised a systems biology approach to understand functional significance.
84 adult psoriatic patients were recruited. Biopsies were taken from lesional (plaque) skin before
and 4-48h after irradiation with equi-erythemogenic doses of 311 and/or 290nm UVB (0.75-3.0
MED). A significant increase in the numbers of apoptotic epidermal cells (active-caspase-3+ cells)
was seen after a single irradiation with 2-3 MEDs 311 nm UVB compared to 2-3 MEDs 290 nm
UVB or untreated psoriasis (median 12/1000, 0/1000 and 0/1000 epidermal cells respectively;
p<0.001). Routine clinical doses of 311nm also induced apoptosis. Immunochemistry and
electron microscopy showed that the vast majority of apoptotic cells were keratinocytes. Live cell
imaging of irradiated cultured keratinocytes and mathematical modelling showed that the rate of
keratinocyte apoptosis observed in vivo was sufficient to account for clearance of psoriasis. Gene
array analysis was used to examine differential gene regulation at these early time-points, prior
to clinical response. Apoptosis and control of cell cycle pathways were affected by 311nm but
not 290nm UVB. CDKN1A (WAF1/p21) showed the greatest fold change (27 fold up-regulation)
following irradiation with 311nm UVB but not 290nm. Together these data provide evidence
that epidermal keratinocyte apoptosis is a key mechanism in psoriasis resolution and identifies
keratinocyte apoptosis as a potential target for future drug development.
Original language | English |
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Article number | 392 |
Pages (from-to) | S66-S66 |
Number of pages | 1 |
Journal | Journal of Investigative Dermatology |
Volume | 131 |
Issue number | Supplement 2 |
DOIs | |
Publication status | Published - Sept 2011 |
Externally published | Yes |
Event | 41st Annual Meeting of the European-Society-for-Dermatological-Research - Barcelona, Spain Duration: 7 Sept 2011 → 10 Sept 2011 |