Basic Research for the Clinical Use of Nuclear Factor-binding DNA Decoy for Inflammatory Skin Diseases

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Thymus and activation-regulated chemokine (TARC/CCL17) is a potent chemokine, deeply associated with the pathogenesis of several inflammatory skin diseases, such as atopic dermatitis and bullous pemphigoid. Production of TARC from HaCaT keraitnocytes was synergistically induced by the stimulated with TNFα and IFNγ. NFkB and p38 are indispensable, EGF receptor was negatively involved, and STAT1 was not involved in this induction. PLA2 inhibitor, MAFP, and leukotrien B4 receptor inhibitor, LY, was also effective in suppressing TARC production. IMD, which was produced to suppress NFkB activation was effective in suppressing TARC production from HaCaT keratinocytes. Mechanical stress, are IL-15 are known to induce new lesions in psoriasis. They induced MAP kinase activation, proliferation, and attenuates apoptosis. Mechanical stress induced EGFR phosphorylation, ERK, and AP-1 activation. IL-15 induced ERK and PI3K activation. Suppression of these signaling molecules could be effective in treating inflammatory skin diseases such as psoriasis. We are planning to utilize these possibilities in vivo experiments.