PMID- 25239864 OWN - NLM STAT- MEDLINE DCOM- 20150305 LR - 20141203 IS - 1872-9142 (Electronic) IS - 0161-5890 (Linking) VI - 63 IP - 2 DP - 2015 Feb TI - Tat-biliverdin reductase A inhibits inflammatory response by regulation of MAPK and NF-kappaB pathways in Raw 264.7 cells and edema mouse model. PG - 355-66 LID - S0161-5890(14)00236-3 [pii] LID - 10.1016/j.molimm.2014.09.003 [doi] AB - Reactive oxygen species (ROS) accumulation induces oxidative stress and cell damage, which then activates several signaling pathways and triggers inflammatory response. Biliverdin is a natural product of heme metabolism which is converted to bilirubin by the enzyme biliverdin reductase A (BLVRA) which also plays a role in antioxidant activity via the ROS scavenging activity of bilirubin. In this study, we examined the anti-inflammatory and anti-apoptotic effects of Tat-BLVRA protein on lipopolysaccharide (LPS)-induced inflammation in Raw 264.7 macrophage cells. Transduction of Tat-BLVRA protein into Raw 264.7 cells and mice ear tissue was tested by Western blot analysis and immunohistochemical analysis. Tat-BLVRA protein was effective in inhibiting mitogen activated protein kinases (MAPKs), Akt and NF-kappaB activation, intracellular ROS production and DNA fragmentation. Also, Tat-BLVRA protein significantly inhibited the expression of cytokines, COX-2, and iNOS. In a 12-O-tetradecanoylphobol 13-acetate (TPA)-induced mouse model, mice ears treated with Tat-BLVRA protein showed decreased ear thickness and weight, as well as inhibited MAPKs activation and cytokine expression. Thus we suggested that Tat-BLVRA protein may provide an effective therapeutic agent for inflammatory skin diseases. CI - Copyright (c) 2014 Elsevier Ltd. All rights reserved. FAU - Kim, Hye Ri AU - Kim HR AD - Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702, South Korea. FAU - Kim, Dae Won AU - Kim DW AD - Department of Biochemistry and Molecular Biology, Research Institute of Oral Sciences, College of Dentistry, Kangnung-Wonju National University, Gangneung 210-702, South Korea. FAU - Jo, Hyo Sang AU - Jo HS AD - Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702, South Korea. FAU - Cho, Su Bin AU - Cho SB AD - Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702, South Korea. FAU - Park, Jung Hwan AU - Park JH AD - Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702, South Korea. FAU - Lee, Chi Hern AU - Lee CH AD - Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702, South Korea. FAU - Choi, Yeon Joo AU - Choi YJ AD - Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702, South Korea. FAU - Yeo, Eun Ji AU - Yeo EJ AD - Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702, South Korea. FAU - Park, Sung Yeon AU - Park SY AD - Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702, South Korea. FAU - Kim, Seung Tae AU - Kim ST AD - Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702, South Korea. FAU - Yu, Yeon Hee AU - Yu YH AD - Department of Anatomy, College of Medicine, Soonchunhyang University, Cheonan-Si 330-090, South Korea. FAU - Kim, Duk-Soo AU - Kim DS AD - Department of Anatomy, College of Medicine, Soonchunhyang University, Cheonan-Si 330-090, South Korea. FAU - Kim, Hyun Ah AU - Kim HA AD - Division of Rheumatology, Department of Internal Medicine, Hallym University Sacred Heart Hospital, Pyongchon, Kyunggido 431-070, South Korea. FAU - Cho, Sung-Woo AU - Cho SW AD - Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul 138-736, South Korea. FAU - Han, Kyu Hyung AU - Han KH AD - Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702, South Korea. FAU - Park, Jinseu AU - Park J AD - Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702, South Korea. FAU - Eum, Won Sik AU - Eum WS AD - Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702, South Korea. Electronic address: wseum@hallym.ac.kr. FAU - Choi, Soo Young AU - Choi SY AD - Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702, South Korea. Electronic address: sychoi@hallym.ac.kr. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140917 PL - England TA - Mol Immunol JT - Molecular immunology JID - 7905289 RN - 0 (Lipopolysaccharides) RN - 0 (NF-kappa B) RN - 0 (Reactive Oxygen Species) RN - 0 (Recombinant Fusion Proteins) RN - 0 (tat Gene Products, Human Immunodeficiency Virus) RN - EC 1.3.- (Oxidoreductases Acting on CH-CH Group Donors) RN - EC 1.3.1.24 (biliverdin reductase) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinases) RN - NI40JAQ945 (Tetradecanoylphorbol Acetate) SB - IM MH - Animals MH - Cell Line MH - Cell Survival/drug effects MH - Disease Models, Animal MH - Edema/pathology/*therapy MH - Humans MH - Inflammation/enzymology/*pathology MH - Lipopolysaccharides/pharmacology MH - Macrophages/drug effects/enzymology/*pathology MH - Male MH - Mice, Inbred ICR MH - Mitogen-Activated Protein Kinases/*metabolism MH - NF-kappa B/*metabolism MH - Oxidative Stress/drug effects MH - Oxidoreductases Acting on CH-CH Group Donors/*genetics/*therapeutic use MH - Proto-Oncogene Proteins c-akt/metabolism MH - Reactive Oxygen Species/metabolism MH - Recombinant Fusion Proteins/isolation & purification MH - Signal Transduction MH - Tetradecanoylphorbol Acetate MH - Transduction, Genetic MH - tat Gene Products, Human Immunodeficiency Virus/metabolism/*therapeutic use OTO - NOTNLM OT - Cytokine OT - Inflammation OT - MAPK OT - Protein therapy OT - ROS OT - Tat-BLVRA EDAT- 2014/09/23 06:00 MHDA- 2015/03/07 06:00 CRDT- 2014/09/21 06:00 PHST- 2014/07/15 00:00 [received] PHST- 2014/08/31 00:00 [revised] PHST- 2014/09/01 00:00 [accepted] PHST- 2014/09/21 06:00 [entrez] PHST- 2014/09/23 06:00 [pubmed] PHST- 2015/03/07 06:00 [medline] AID - S0161-5890(14)00236-3 [pii] AID - 10.1016/j.molimm.2014.09.003 [doi] PST - ppublish SO - Mol Immunol. 2015 Feb;63(2):355-66. doi: 10.1016/j.molimm.2014.09.003. Epub 2014 Sep 17.