title: Transduced PEP-1-FK506BP ameliorates corneal injury in Botulinum toxin A-induced dry eye mouse model.
abstract: FK506 binding protein 12 (FK506BP) belongs to a family of immunophilins, and is involved in multiple biological processes. However, the function of FK506BP in corneal disease remains unclear. In this study, we examined the protective effects on dry eye disease in a Botulinum toxin A (BTX-A) induced mouse model, using a cell-permeable PEP-1-FK506BP protein. PEP-1-FK506BP efficiently transduced into human corneal epithelial cells in a time- and dose-dependent manner, and remained stable in the cells for 48 h. In addition, we demonstrated that topical application of PEP-1-FK506BP was transduced into mouse cornea and conjunctiva by immunohistochemistry. Furthermore, topical application of PEP-1-FK506BP to BTX-A-induced mouse model markedly inhibited expression levels of pro-inflammatory cytokines such as interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and macrophage inhibitory factor (MIF) in corneal and conjunctival epithelium. These results suggest PEP-1-FK506BP as a potential therapeutic agent for dry eye diseases.
authors: Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon 200-702, Korea.
authors: Dae Won
authors: DW
authors: Kim
authors: Sung Ho
authors: SH
authors: Lee
authors: Sae Kwang
authors: SK
authors: Ku
authors: Soo Hyun
authors: SH
authors: Cho
authors: Sung-Woo
authors: SW
authors: Cho
authors: Ga Hyeon
authors: GH
authors: Yoon
authors: Hyun Sook
authors: HS
authors: Hwang
authors: Jinseu
authors: J
authors: Park
authors: Won Sik
authors: WS
authors: Eum
authors: Oh-Shin
authors: OS
authors: Kwon
authors: Soo Young
authors: SY
authors: Choi
mesh_terms: D000287:Administration, Topical; D000818:Animals; D019274:Botulinum Toxins, Type A / Q000633:toxicity; D002460:Cell Line; D003228:Conjunctiva / Q000187:drug effects / Q000378:metabolism; D003315:Cornea / Q000187:drug effects* / Q000378:metabolism; D003543:Cysteamine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D004195:Disease Models, Animal; D015352:Dry Eye Syndromes / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D007150:Immunohistochemistry; D053583:Interleukin-1beta / Q000378:metabolism; D019402:Macrophage Inflammatory Proteins / Q000378:metabolism; D051379:Mice; D010455:Peptides / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000494:pharmacology / Q000627:therapeutic use; D022021:Tacrolimus Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D014161:Transduction, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D053583:Interleukin-1beta; D019402:Macrophage Inflammatory Proteins; C503924:Pep-1 peptide; D010455:Peptides; D011993:Recombinant Fusion Proteins; D014409:Tumor Necrosis Factor-alpha; D003543:Cysteamine; D019274:Botulinum Toxins, Type A; D022021:Tacrolimus Binding Proteins