title: PLAG (1-Palmitoyl-2-Linoleoyl-3-Acetyl-rac-Glycerol) Modulates Eosinophil Chemotaxis by Regulating CCL26 Expression from Epithelial Cells.
abstract: Increased number of eosinophils in the circulation and sputum is associated with the severity of asthma. The respiratory epithelium produces chemokine (C-C motif) ligands (CCL) which recruits and activates eosinophils. A chemically synthesized monoacetyl-diglyceride, PLAG (1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol) is a major constituent in the antlers of Sika deer (Cervus nippon Temminck) which has been used in oriental medicine. This study was aimed to investigate the molecular mechanism of PLAG effect on the alleviation of asthma phenotypes. A549, a human alveolar basal epithelial cell, and HaCaT, a human keratinocyte, were activated by the treatment of interleukin-4 (IL-4), and the expression of chemokines, known to be effective on the induction of eosinophil migration was analyzed by RT-PCR. The expression of IL-4 induced genes was modulated by the co-treatment of PLAG. Especially, CCL26 expression from the stimulated epithelial cells was significantly blocked by PLAG, which was confirmed by ELISA. The transcriptional activity of signal transducer and activator of transcription 6 (STAT6), activated by IL-4 mediated phosphorylation and nuclear translocation, was down-regulated by PLAG in a concentration-dependent manner. In ovalbumin-induced mouse model, the infiltration of immune cells into the respiratory tract was decreased by PLAG administration. Cytological analysis of the isolated bronchoalveolar lavage fluid (BALF) cells proved the infiltration of eosinophils was significantly reduced by PLAG. In addition, PLAG inhibited the migration of murine bone marrow-derived eosinophils, and human eosinophil cell line, EoL-1, which was induced by the addition of A549 culture medium.
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: Jinseon
authors.initials: J
authors.lastname: Jeong
authors.affiliation: Biomedical Translational Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Republic of Korea.
authors.forename: Young-Jun
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: ENZYCHEM Lifesciences, KAIST-ICC, Daejeon 305-732, Republic of Korea.
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.
authors.forename: Yong-Jae
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: Department of Pathology, Eulji University School of Medicine, Daejeon 302-120, Republic of Korea.
authors.forename: Joo Heon
authors.initials: JH
authors.lastname: Kim
authors.affiliation: ENZYCHEM Lifesciences, KAIST-ICC, Daejeon 305-732, Republic of Korea.
authors.forename: Ki-Young
authors.initials: KY
authors.lastname: Sohn
authors.affiliation: ENZYCHEM Lifesciences, KAIST-ICC, Daejeon 305-732, Republic of Korea.
authors.forename: Heung-Jae
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: ENZYCHEM Lifesciences, KAIST-ICC, Daejeon 305-732, Republic of Korea.
authors.forename: Yong-Hae
authors.initials: YH
authors.lastname: Han
authors.affiliation: ENZYCHEM Lifesciences, KAIST-ICC, Daejeon 305-732, Republic of Korea.
authors.forename: Saeho
authors.initials: S
authors.lastname: Chong
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: Jae Wha
authors.initials: JW
authors.lastname: Kim
mesh_terms: D000818:Animals; D001249:Asthma / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D000075906:Chemokine CCL26; D019742:Chemokines, CC / Q000235:genetics* / Q000276:immunology; D002633:Chemotaxis / Q000187:drug effects*; D003670:Deer; D004075:Diglycerides / Q000494:pharmacology / Q000627:therapeutic use*; D004804:Eosinophils / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D004847:Epithelial Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D015847:Interleukin-4 / Q000276:immunology; D008807:Mice, Inbred BALB C
chemical_list: C488567:1-palmitoyl-2-linoleoyl-3-acetyl-rac glycerol; C120429:CCL26 protein, human; D000075906:Chemokine CCL26; D019742:Chemokines, CC; D004075:Diglycerides; D015847:Interleukin-4