The Effect of TNF-alpha and INF-gamma on the Telomerase Activity of Cultured Human Keratinocyte

ABSTRACT

Psoriasis is a chronic inflammatory skin disease characterized by hyperproliferation and abnormal differentiation of the lesional epidermis. In pathogenesis, inflammatory cytokines such as TNF-alpha and IFN-gamma from infiltrated T-cells seem to act a central role. Although many chronic inflammatory conditions can lead to cancer development, there is no evidence of increased incidence of cancer in psoriatic skin lesion. Telomerase is an enzyme-reverse transcriptase that protects chromosomes from degradation by stabilizing telomere length. Recent studies suggest that telomerase activity may be responsible for some part of nonmalignant proliferatory skin disease. In addition, there is evidence that telomerase activity is related with proliferation and differentiation of keratinocyte. In this experiment, we tried to evaluate the effect of TNF-alpha and IFN-gamma to the telomerase activity and its differential effect thought the passage. The results showed increased telomerase activity according to stimulation and this extent was different from the various passage. These results suggest that the key cytokines of psoriasis, namely, TNF-alpha and IFN-gamma increase telomerase activity at proliferative cells, which could contribute to hyperproliferation and abnormal differentiation of lesional keratinocyte. Moreover, this increased telomerase activity could partially explain the cancer incidence of psoriasis that is not increased compared to the normal population.