title: Effects of pergolide mesylate on transduction efficiency of PEP-1-catalase protein.
abstract: The low transduction efficiency of various proteins is an obstacle to their therapeutic application. However, protein transduction domains (PTDs) are well-known for a highly effective tool for exogenous protein delivery to cells. We examined the effects of pergolide mesylate (PM) on the transduction of PEP-1-catalase into HaCaT human keratinocytes and mice skin and on the anti-inflammatory activity of PEP-1-catatase against 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation using Western blot and histological analysis. PM enhanced the time- and dose-dependent transduction of PEP-1-catalase into HaCaT cells without affecting the cellular toxicity. In a mouse edema model, PEP-1-catalase inhibited the increased expressions of inflammatory mediators and cytokines such as cyclooxygenase-2, inducible nitric oxide synthase, interleukin-6 and -1β, and tumor necrosis factor-α induced by TPA. On the other hand, PM alone failed to exert any significant anti-inflammatory effects. However, the anti-inflammatory effect of co-treatment with PEP-1-catalase and PM was more potent than that of PEP-1-catalase alone. Our results indicate that PM may enhance the delivery of PTDs fusion therapeutic proteins to target cells and tissues and has potential to increase their therapeutic effects of such drugs against various diseases.
authors.affiliation: Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702, Republic of Korea.
authors.forename: Eun Jeong
authors.initials: EJ
authors.lastname: Sohn
authors.forename: Dae Won
authors.initials: DW
authors.lastname: Kim
authors.forename: Young Nam
authors.initials: YN
authors.lastname: Kim
authors.forename: So Mi
authors.initials: SM
authors.lastname: Kim
authors.forename: Soon Sung
authors.initials: SS
authors.lastname: Lim
authors.forename: Tae-Cheon
authors.initials: TC
authors.lastname: Kang
authors.forename: Hyeok Yil
authors.initials: HY
authors.lastname: Kwon
authors.forename: Duk-Soo
authors.initials: DS
authors.lastname: Kim
authors.forename: Sung-Woo
authors.initials: SW
authors.lastname: Cho
authors.forename: Kyu Hyung
authors.initials: KH
authors.lastname: Han
authors.forename: Jinseu
authors.initials: J
authors.lastname: Park
authors.forename: Won Sik
authors.initials: WS
authors.lastname: Eum
authors.forename: Hyun Sook
authors.initials: HS
authors.lastname: Hwang
authors.forename: Soo Young
authors.initials: SY
authors.lastname: Choi
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000378:metabolism*; D002374:Catalase / Q000008:administration & dosage / Q000378:metabolism*; D002460:Cell Line; D003543:Cysteamine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism; D003872:Dermatitis / Q000188:drug therapy*; D016503:Drug Delivery Systems; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010455:Peptides / Q000008:administration & dosage / Q000378:metabolism*; D010479:Pergolide / Q000494:pharmacology*; D021381:Protein Transport / Q000187:drug effects; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000031:analogs & derivatives / Q000633:toxicity
chemical_list: C554292:12-O-tetradecanoylphorbol-1,3-acetate; D000894:Anti-Inflammatory Agents, Non-Steroidal; C503924:Pep-1 peptide; D010455:Peptides; D011993:Recombinant Fusion Proteins; D010479:Pergolide; D003543:Cysteamine; D002374:Catalase; C558128:PEP-1-catalase fusion protein; D013755:Tetradecanoylphorbol Acetate