title: Genkwadaphnin promotes leukocyte migration by increasing CD44 expression via PKD1/NF-κB signaling pathway.
abstract: Genkwadaphnin (GD), an extract from the flower buds of Daphne genkwa Siebold & Zucc. (Thymelaeaceae) has been reported a significant anti-leukemic activity. However, its functional mechanism has not been defined well. To study the biological mechanism of GD function, we have investigated whether GD affects CD44 expression, which has a role in the regulation of immune cell motilities, and identified the related signaling pathways. GD treatment induced the increase of CD44 expression in a time- and concentration-dependent manner, which was specific for immune cells. GD activated PKD1/NF-κB signaling to induce CD44 expression, and resulted in the increased migration of K562 cells. In invasion assay, cell migratory ability was induced by GD and the transfection with CD44-specific short hairpin RNA resulted in reduction of its cell migration. GD treated human peripheral blood mononuclear cell (PBMC) were also shown the increased CD44 expression and migration. These data suggest that the induction of CD44 expression by GD treatment promotes immune cell transmigration resulting in the enhanced innate immunity.
authors.affiliation: Biomedical Translational Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Republic of Korea; Department of Functional Genomics, University of Science and Technology, Daejeon 305-806, Republic of Korea.
authors.forename: Nina
authors.initials: N
authors.lastname: Yoo
authors.affiliation: Biomedical Translational Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Republic of Korea.
authors.forename: Ha-Reum
authors.initials: HR
authors.lastname: Lee
authors.affiliation: Biomedical Translational Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Republic of Korea.
authors.forename: Jang-Mi
authors.initials: JM
authors.lastname: Son
authors.affiliation: Biomedical Translational Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Republic of Korea.
authors.forename: Ho-Bum
authors.initials: HB
authors.lastname: Kang
authors.affiliation: Genome Structure Research Center, Genome Institute, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Republic of Korea.
authors.forename: Hee Gu
authors.initials: HG
authors.lastname: Lee
authors.affiliation: Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Republic of Korea.
authors.forename: Suk Ran
authors.initials: SR
authors.lastname: Yoon
authors.affiliation: Enzychem Lifesciences, 103-6, KAIST-ICC F741, Munjidong, Daejeon 305-732, Republic of Korea. Electronic address: syyoon@enzychem.com.
authors.forename: Sun Young
authors.initials: SY
authors.lastname: Yoon
authors.affiliation: Biomedical Translational Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Republic of Korea; Department of Functional Genomics, University of Science and Technology, Daejeon 305-806, Republic of Korea. Electronic address: wjkim@kribb.re.kr.
authors.forename: Jae Wha
authors.initials: JW
authors.lastname: Kim
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D032364:Daphne / Q000276:immunology; D004224:Diterpenes / Q000494:pharmacology*; D057809:HEK293 Cells; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics / Q000378:metabolism*; D007113:Immunity, Innate; D020014:K562 Cells; D007938:Leukemia / Q000188:drug therapy*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000502:physiology*; D008516:Medicine, Chinese Traditional; D016328:NF-kappa B / Q000378:metabolism; D010936:Plant Extracts; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D050396:TRPP Cation Channels / Q000378:metabolism; D020298:U937 Cells; D015854:Up-Regulation
chemical_list: D000970:Antineoplastic Agents; D004224:Diterpenes; D018960:Hyaluronan Receptors; D016328:NF-kappa B; D010936:Plant Extracts; D034741:RNA, Small Interfering; D050396:TRPP Cation Channels; C036412:genkwadaphnin
keywords: CD44; Genkwadaphnin; Leukocyte; Migration; NF-κB; PKD1