More MS news articles for Mar 2002

New Strategy for Treating Psoriasis

28th Feb, 2002

Dexamethasone and other steroids used for treating psoriatic skin inflammation probably act in part by inducing I-kB, thus preventing NF-kB from reaching the nucleus and trans-activating its many target genes, including those involved in T cell-dependent inflammation. Zollner and colleagues now propose a different means to this same end in a report published in the Journal of Clinical Investigation.

Since the proteasome is responsible for the regulated turnover of I-kB, proteasome inhibitors might also alleviate psoriasis by blocking NF-kB activation. Indeed, such inhibitors have already been used successfully in animal models of rheumatoid arthritis and multiple sclerosis, conditions that (like psoriasis) are thought to result from T cell exposure to bacterial antigens.

Working with human psoriatic skin tissue engrafted onto mice, Zollner et al. confirm that a known bacterial superantigen can provoke psoriatic lesions. They find that proteasome inhibition prevents NF-kB activation in cultured T cells and that it blocks expression of adhesive surface molecules required for T cell homing. In engrafted mice, the inhibitor prevents psoriasis as efficiently as dexamethasone does.

These different agents, which can each increase I-kB levels, presumably both silence NF-kB target genes in vivo. In addition, however, proteasome inhibitors might exert other beneficial effects, since they undoubtedly stabilizes a variety of short-lived proteins, some of which could block disease progression by other mechanisms.

Source: Journal of Clinical Investigation

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