促炎细胞因子
超氧化物歧化酶
炎症
氧化应激
信号转导
12-O-十四烷基佛波醇-13-乙酸酯
化学
药理学
肿瘤坏死因子α
过氧化氢酶
蛋白激酶C
免疫学
分子生物学
生物化学
生物
佛波酯
作者
Ha Yong Song,Ji Ae Lee,Sung Mi Ju,Ki‐Yeon Yoo,Moo Ho Won,Hyung‐Joo Kwon,Won Sik Eum,Sang Ho Jang,Soo Young Choi,Jinseu Park
标识
DOI:10.1016/j.bcp.2007.11.015
摘要
A domain (RKKRRQRRR) derived from HIV-1 Tat is one of the most efficient protein transduction domains (PTD) for delivering macromolecules including proteins into cells and tissues. Antioxidant enzymes such as superoxide dismutase (SOD) and catalase are major cellular defenses against oxidative stress which results in various diseases including skin inflammation. In this study, we examined the effect of SOD fused with HIV-1 Tat PTD (Tat-SOD) on TPA-induced skin inflammation in mice. Topical application of Tat-SOD to mice ears 1 h after TPA application once a day for 3 days dose-dependently inhibited TPA-induced ear edema in mice. Topical application on mice ears of Tat-SOD also suppressed TPA-induced expression of proinflammatory cytokines such as TNF-α, IL-1β, and IL-6 as well as cyclooxygenase-2 (COX-2) and production of PGE2. Furthermore, topical application of Tat-SOD resulted in significant reduction in activation of NF-κB and mitogen-activated protein kinases (MAPK) in the mice ears treated with TPA. These data demonstrates that Tat-SOD inhibits TPA-induced inflammation in mice by reducing the levels of expression of proinflammatory cytokines and enzymes regulated by the NF-kappaB and MAPK and can be used as a therapeutic agent against skin inflammation related to oxidative damage.
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