Benzer, A.

Durante, M.

Fournier, C.

Kovacs, M.

Podda, M.

Simoniello, P.

Thönnes, E.

Wiedemann, J.

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Radiation response related to inflammation and differentiation in human skin∗J. Wiedemann1,2, P. Simoniello1, E. Tho¨nnes1, A. Benzer1, M.Durante1,2, M. Kovacs4, M. Podda4, andC. Fournier1,31GSI, Darmstadt, Germany; 2TU Darmstadt, Germany; 3Hochschule Darmstadt, Germany; 4Department ofDermatology, Darmstadt HospitalIntroductionThe balance between apoptosis, proliferation and differ-entiation is important for the homeostasis of healthy skin[1]. In psoriatic skin this balance is disturbed and shiftedin the direction of proliferation [2].The symptoms of psori-asis can be alleviated by irradiation with low intensities ofUV-light [3] or low doses of ionizing irradiation, such asalpha-particels emitted from a radon source [4]. These ef-fects of UV exposure in skin are quite well understood [3],whereas alterations in skin induced by low doses of ioniz-ing irradiation which explain the clinical effectiveness ofradon treatments remain to be elucidated.We investigated if irradiation with low and clinically usedfractionated doses shifts the disturbed balance of apoptosis,proliferation and differentiation back to a normal level byenhancing apoptosis and/or reducing proliferation.Material and MethodsHuman full-thickness skin equivalents (EFT400; Mat-Tek; Ashland) were irradiated using low versus high andsingle versus fractionated X-ray doses. Samples werefixed 3 days after irradiation and processed for immuno-histchemistry. Proliferation was assessed microscopicallyand Ki67+ cells per field of view were counted. To anal-yse the status of differentiation sections were stained withHematoxylin and Eosin.Results and DiscussionHistological analysis (H&E staining) shows that afterlow dose X-ray irradiation the basal cells loose their pal-isadic shape and become more rounded up. This effect ismore pronounced after a single dose of 0,5 Gy comparedto a fractionated irradiation with 3x 0,17 Gy. The cobble-stoned morphology can be related to proliferation of thebasal cells which can be a sign of a faster or impaired dif-ferentiation process. An enhanced proliferation in the basallayer after a low dose of irradiation could be confirmedby quantification of Ki67 (Figure 2) but was not observedfor high X-ray doses like 10 Gy (data not shown). Inter-estingly, also for a fractionation of 0,5 Gy in 3 doses of0,17 Gy this effect didn’t occure pointing to that a singletreshold dose has to be delivered to trigger proliferation .In addition to the observed changes in morphology of thebasal cells which have an impact on tissue organisation and∗Work supported by GREWIS No. 02NUK017A; DFG (GRK 1657)and HGS-HIRe.Figure 1: H&E staining of sections from skin equivalents.Changes in the shape of the basal cells (green) and the strat-ification (red) are indicated with arrows. Pictures a’ to c’show a magnification of the basal cellsFigure 2: (A) Ki67 staining of skin equivalents. Prolifer-ating cells are labeled in pink and indicated with an arrow.(B) Statistical analysis of Ki67 stainingthe enhanced proliferation for a low X-ray dose we couldshow in previous studies that there is no enhancement ofcell death (apoptosis and necrosis) after low dose of irradi-ation. This argues against a irradiation induced shift to en-hanced apoptosis and reduces proliferation after low doses.These effects has to be further investigated in a model sys-tem which mimics the inflammatory state of psoriatic skin.References[1] P. Kolarsick et al.,J Dermatol Nurses Assoc, Volume 3, 2011[2] M. Lowes et al., NATURE Vol 445—22 February 2007,doi:10.1038/nature05663[3] K. Stein., J Dermatolog Treat.. 2008; 19: 141–145[4] P. Deetje et al., Verlag Dr. Kovac, 2005APPA-HEALTH-26 GSI SCIENTIFIC REPORT 2014318 DOI:10.15120/GR-2015-1-APPA-HEALTH-26

Radiation response related to inflammation and differentiation in human skin

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Radiation response related to inflammation and differentiation in human skin

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