Decreased growth inhibition by recombinant gamma interferon is associated with increased transforming growth factor-α production in keratinocytes cultured from psoriatic lesions

摘要: Keratinocytes from involved psoriatic plaques (PP), uninvolved, clinically symptomless skin of patients (PN) and normal healthy (NN) have been cultured in a low calcium serum free system for multiple passages. In this way, the keratinocytes were removed microenvironmental factors present skin. While basal rate proliferation PP, PN NN was not different, PP cells produced more transforming growth factor-alpha (TGF-alpha) than cells, antiproliferative response to gamma interferon (IFN-gamma), product activated T lymphocytes, reduced. We studied IFN-gamma because it can inhibit keratinocytes, induce their differentiation appearance two immunoregulatory cell surface molecules, HLA-DR intercellular adherence molecule-I (ICAM-I), another epithelial system, epidermal factor (EGF) modulates activity. The mean effects at 50,200, 500 U/ml group (n = 10) less compared 11); P 0.001, while 5) had dramatic, but statistically significant, reduction inhibition by only 200 cells; 0.05 0.01, respectively. amount TGF-alpha secreted five different individuals significantly greater keratinocyte cultures. addition, induced lesser extent isolated atopic dermatitis Sezary syndrome similar keratinocytes. contrast its differential on production proliferation, amounts ICAM-I Thus, there dissociation between immunomodulatory IFN-gamma. These results support our previous hypothesis that hyperproliferation altered is linked an responsiveness Moreover, these provide vitro correlate vivo observation increased levels plaques. A new pathophysiological model understand psoriasis proposed which integrates observations involving TGF-alpha. This experimental approach also provides dissect biochemical pathways importance psoriasis.