Topical transduction of superoxide dismutase mediated by HIV-1 Tat protein transduction domain ameliorates 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation in mice.
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 1h 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-alpha, IL-1beta, and IL-6 as well as cyclooxygenase-2 (COX-2) and production of PGE(2). Furthermore, topical application of Tat-SOD resulted in significant reduction in activation of NF-kappaB 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.
Song
Ha Yong
HY
Department of Biomedical Science, Hallym University, 1 Okchun-dong, Chunchon, Kangwon-Do 200-702, Republic of Korea.
Lee
Ji Ae
JA
Ju
Sung Mi
SM
Yoo
Ki-Yeon
KY
Won
Moo Ho
MH
Kwon
Hyung-Joo
HJ
Eum
Won Sik
WS
Jang
Sang Ho
SH
Choi
Soo Young
SY
Park
Jinseu
J
D000279:Administration, Cutaneous; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D015232:Dinoprostone / Q000276:immunology; D015497:HIV-1; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D020928:Mitogen-Activated Protein Kinases / Q000276:immunology; D052247:Nitric Oxide Synthase Type II / Q000276:immunology; D017434:Protein Structure, Tertiary; D017382:Reactive Oxygen Species / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000627:therapeutic use*; D012871:Skin Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology; D013482:Superoxide Dismutase / Q000235:genetics / Q000627:therapeutic use*; D013755:Tetradecanoylphorbol Acetate; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000627:therapeutic use*
D000893:Anti-Inflammatory Agents; D016207:Cytokines; D017382:Reactive Oxygen Species; D011993:Recombinant Fusion Proteins; D054322:tat Gene Products, Human Immunodeficiency Virus; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D013482:Superoxide Dismutase; D020928:Mitogen-Activated Protein Kinases; D015232:Dinoprostone; D013755:Tetradecanoylphorbol Acetate