Cyclin D1, B and A expression and cell turnover in psoriatic skin lesions before and after cyclosporin treatment.
BACKGROUND
Cyclosporin induces a dramatic reversal to normality in psoriatic lesions, with a reduction of inflammatory infiltrate and epidermal proliferation. It is known that the cell cycle and cell proliferation are regulated by the sequential activation of cyclin-dependent kinase/cyclin complexes.


OBJECTIVE
We evaluated epidermal cell turnover and thickness, as well as the expression of cyclins D1, B and A in psoriatic skin before and after therapy with cyclosporin.


METHODS
Epidermal thickness, mitotic and apoptotic indices (MI, AI), as well as the percentages of epidermal cell nuclei positive for Ki-67 and cyclins D1, B and A were calculated. Cytoplasmic positivity to cyclin B was also evaluated.


RESULTS
After 6 weeks of therapy, we observed a clinical improvement of the disease and normalization of the epidermis. Epidermal thickness and Ki-67-, cyclins B- and A-positive nuclei percentage were significantly higher before therapy than after (0.52 +/- 0.05 mm vs. 0.21 +/- 0.03 mm, P < 0.001; 19 vs. 2.6, 19 vs. 3, and 12 vs. 1, respectively; P < 0.0005); cytoplasmic positivity to cyclin B was slightly higher before therapy (score 3 vs. 2-3). Cyclin D1 was negative or expressed in a low percentage of nuclei in psoriasis before therapy (0.78), whereas it was always negative after therapy. MI was 0.15 before therapy, whereas mitoses were almost absent afterwards. Apoptoses were undetectable before therapy, whereas a few apoptoses were observed after treatment (AI = 0.4).


CONCLUSIONS
Overexpression of cyclins B and A, rather than D1 seems to characterize psoriasis. Their evaluation could provide further insights in understanding the development of this disorder and could be used to verify the efficacy of currently used therapies as well as future ones.
Miracco
C
C
Institute of Pathological Anatomy and Histology, University of Siena, Via delle Scotte 6, 53100-Siena, Italy. miracco@unisi.it
Pellegrino
M
M
Flori
M L
ML
Vatti
R
R
Materno
M
M
Andreassi
L
L
D000328:Adult; D015415:Biomarkers / Q000032:analysis; D002455:Cell Division / Q000187:drug effects; D019925:Cyclin A / Q000378:metabolism; D019926:Cyclin B / Q000378:metabolism; D019938:Cyclin D1 / Q000378:metabolism; D016213:Cyclins / Q000378:metabolism*; D016572:Cyclosporine / Q000627:therapeutic use*; D003879:Dermatologic Agents / Q000627:therapeutic use*; D004817:Epidermis / Q000378:metabolism / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011565:Psoriasis / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology
D015415:Biomarkers; D019925:Cyclin A; D019926:Cyclin B; D016213:Cyclins; D003879:Dermatologic Agents; D007166:Immunosuppressive Agents; D019938:Cyclin D1; D016572:Cyclosporine