MAP KINASE ABNORMALITIES IN HYERPROLIFERATIVE CULTURED FIBROBLASTS FROM PSORIATIC SKIN

Several studies indicate that dermal fibroblasts have a specific role in the pathophysiology of psoriasis. We have previously found that cul tured fibroblasts from psoriatic patients are hyperproliferative and h ave low cyclic AMP-dependent protein kinase activity. In this study, w e observed that these cells are also larger than normal. Given the key role of mitogen-activated protein kinases (MAPK) in the regulation of cell proliferation and cytoskeleton function, we characterized MAPK i n psoriatic fibroblasts and in normal fibroblasts. Serum and platelet- derived growth factor treatment of serum-deprived fibroblasts led to a larger increase in MAPK activity in psoriatic cells than in normal ce lls. We then purified MAPK by ion-exchange chromatography. MAPK activi ty was again found to be significantly higher in psoriatic fibroblasts than in normal cells, both when deprived of serum (p < 0.01) and when stimulated with serum (p < 0.05). Interestingly, 8-bromo-cAMP treatme nt inhibited serum-stimulated MAPK phosphorylation in normal fibroblas ts but had no effect in psoriatic fibroblasts. We observed a temporal variation in nuclear localization of phosphorylated MAPK in cultured f ibroblasts stimulated by either serum or platelet-derived growth facto r. No difference in the localization of phosphorylated MAPK in normal and psoriatic skins was found. Psoriatic fibroblasts are the first exa mple of a MAPK pathway abnormality in large human benign hyperprolifer ative cells.