Psoriasis is a chronic inflammatory skin condition that varies in severity, which is an important implication in terms of medical costs and treatment strategies. Various factors such as genetic com­ponents, environmental factors, microorganism and immunologic reactions seem to play a role in the disease development. The skin lesion of psoriasis is characterized by focal formation of inflamed, raised plaques that constantly shed scales. Previously, it was assumed that keratinocyte hyperproliferation asso­ciated with abnormal epidermal differentiation was the primary cause of psoriasis4,14. However, it is now conceptualized that T-cell mediated immunologic reaction play a central role during its pathogenesis, as the trigger for keratinocyte hyperproliferation and incomplete abnormal differentiation. During this process, TH1-type cytokines, such as IFN-y and TNF-a are known to play an important role and downregulation of epidermal IFN-y and TNF-a level has been shown to correlated with clinical improvement of psoriasis .

In this study, we treated cultured human keratino- cyte with IFN-y and/or TNF-a and measured the number of population doubling to evaluate indirectly which stage or compartment of cells are mostly affected. In the previous report about the effect of TNF-a in epidermal keratinocyte, it showed the inhibitory effect on cell proliferation. IFN-y also showed strong inhibitory effects on cell proliferation and these effects showed synergy in present action of TNF-a. Our results showed significant in­hibitory effects on cell proliferation in the early passage (P0, P1) of serial cultures. Considering early passage contains more proliferatory cells such as stem cells and transit amplifying cells, we could postulate that those effects of TNF-a and TNF-y affect mostly the proliferatory cell components. However, some specific methods using cell marker or certain proteins seemed to be necessary to find which cell com­ponents were mostly affected. vardenafil 20 mg

Telomere serves essential roles in preventing checkpoint activation and it maintains chromosomal stability. Telomerase is an enzyme-reverse trans- criptase that stabilizes chromosomal length. It serves multiple functions in preserving chromosome stability; including protecting the end of chromosomes from degradation and preventing chromosomal end fusion. Through these actions, telomerase was known to play a central role in series of cellular biology such as proliferation, differentiation and apoptosis. In the previous reports, telomerase was also known to play a central role in carcinogenesis. During the early stages of carcinogenesis, telomere shortening leads to loss of telomerase capping func­tion, chromosomal fusion and chromosomal insta­bility. In this stage, if additional pressures exist to lose p53 function to allow further cell proliferation in the presence of chromosomal instability, it could finally result in cellular transformation and initiation of cancer. Increased telomerase activity was reported in not only malignant cancers, but also nonmalignant skin conditions such as psoriatic skin lesions.

Chronic inflammatory diseases are also known to contribute to carcinogenesis. However, the con­version of a psoriatic plaque to cancer is very rare.
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Considering all the above reports, we hypothe­sized that TNF-a and IFN-y, key cytokines on the psoriasis, might result in the increased telomerase activity, and this elevated telomerase activity could partially explain the reason why conversion of psoriatic plaque to cancer is very rare. To evaluate the above hypothesis, we investigated the effect of TNF-a and IFN-y on telomerase in the keratino­cyte. To examine which compartment of cells are more sensitive, we treated human keratinocytes form various passages with TNF-a and/or IFN-y. The results showed significant increased telomerase activity in the early passage of cultures and these effects became faint during the passage. Elevated relative telomerase activity was more significant when cells were treated with TNF-a and IFN-y together. Those results were similar to previous reports about the synergic effect of TNF-a with IFN- y in the induction of keratinocyte apoptosis. Interestingly, our results about the pattern of increased telomerase activity seemed to parallel with the inhibitory effect of TNF-a and IFN-y on cul­tured human keratinocyte. In concordance with our results, we could postulate that TNF-a and IFN-y elevate the telomerase activity in the psoriatic skin lesions which is partially responsible for the reason of its rare cancer incidence. Moreover, if we consider that reports about epidermal differentiation, apoptosis and senescence share a series of common pathways, our results could also help explain the abnormal differentiation of the psoriatic skin lesions.