Abstract:

Objective To investigate the susceptibility of epidermal cells to ultraviolet A （UVA）- induced apoptosis in dopachrome tautomerase knockout （Dct-/-） mice versus wildtype C57BL/6J mice. Methods High titer of anti-Ro/SSA-positive sera collected from three patients with SLE and typical cutaneous photosensitivity were intraperitoneally injected into both Dct-/- and wildtype mice, which were then chronically exposed to UVA irradiation at a single dose of 10 J/cm2 three times a week for two weeks. Then, UVA-irradiated tail skin was excised from each mouse, embedded with paraffin, cut into 4 to 5-μm sections followed by hematoxylin/eosin staining and terminal deoxynucleotidyl transferase nick end labeling （TUNEL）, respectively, for the counting of sunburn cells （SBC） and apoptotic cells. Results After chronic UVA exposure, the number of SBC and TUNEL-positive cells per 100 epithelial cells was significantly higher in serum-injected Dct-/- mice than in serum-injected wildtype mice （14 ± 1.0 vs 7 ± 0.6, 62 ± 2.7 vs 30 ± 1.6, both P < 0.05）. A significant decrease was also observed in the number of SBC （6 ± 0.9 per 100 epithelial cells） and TUNEL-positive cells （42 ± 2.5 per 100 epithelial cells） in uninjected Dct-/- mice compared with those of serum-injected Dct-/- mice （both P < 0.05）. Conclusions The deficiency of Dct gene increases the susceptibility of epidermal cells to UVA-induced apoptosis under the presence of anti-Ro/SSA antibody, which potentially contributes to the development of anti-Ro/SSA antibody-mediated photosensitivity in SLE.

Key words: Anti-Ro/SSA antibody, Apoptosis, Photophobia, Genes, Dct