ABERRANT TIMING IN EPIDERMAL EXPRESSION OF INDUCIBLE NITRIC-OXIDE SYNTHASE AFTER UV IRRADIATION IN CUTANEOUS LUPUS-ERYTHEMATOSUS

Photosensitivity is a main criterion for the diagnosis of systemic lup us erythematosus (LE), and ultraviolet (UV) irradiation plays a key ro le in the pathogenesis of cutaneous LE. Patients with a tentative diag nosis of LE are routinely tested for skin lesion development after exp erimental UV irradiation, providing an ideal opportunity to evaluate e arly, preclinical events involved in the pathogenesis of LE. Several r eports have shown expression of the cytokine-inducible nitric oxide sy nthase (iNOS) in autoimmune diseases. Therefore, we investigated the r ole of iNOS expression at mRNA and protein level in the pathogenesis o f LE lesions. Skin biopsies from patients with different subtypes of L E were examined, and iNOS expression was found in six of 18 biopsies f rom cutaneous LE patients and two of three biopsies from systemic LE p atients. In biopsies taken 4-20 d after UV irradiation, epidermal iNOS expression was seen in all patients (n 10) after UVB and in four of 1 0 patients provoked by UVA. In healthy controls (n 8) epidermal iNOS e xpression was detected 24 h after UV irradiation, persisting for anoth er day before subsiding on day 3, In LE patients (n = 8) the exact rev erse situation was seen: an iNOS-specific signal was undetectable in k eratinocytes for 2 d after UV irradiation, but became positive on day 3 and persisted for up to 25 d in the evolving skin lesions. Our findi ngs demonstrate a time-restricted, UV-induced iNOS expression in human skin; moreover, the results indicate that both the kinetics of iNOS i nduction as well as the time span of local iNOS expression may be crit ical to the development of cutaneous LE lesions.