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

趋化因子TARC/CCL 17是一种有效的趋化因子，与特应性皮炎和大疱性类天疱疮等炎症性皮肤病的发病机制密切相关。TNFα和IFNγ协同诱导HaCaT角膜基质细胞产生TARC。NFkB和p38是不可缺少的，EGF受体负性参与，而STAT 1不参与该诱导。PLA 2抑制剂MAFP和白三烯B4受体抑制剂LY也能有效抑制TARC的产生。产生IMD以抑制NFkB活化，其有效抑制HaCaT角质形成细胞的TARC产生。已知机械应力是IL-15在银屑病中诱导新的病变。它们诱导MAP激酶活化、增殖并减弱凋亡。机械应力诱导EGFR磷酸化、ERK和AP-1活化。IL-15诱导ERK和PI 3 K活化。抑制这些信号分子可能有效地治疗炎症性皮肤病，如牛皮癣。我们计划在体内实验中利用这些可能性。

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.