title: Inhibition of foreign body giant cell formation by 4- hexylresorcinol through suppression of diacylglycerol kinase delta gene expression.
abstract: Grafted macromolecules often induce granuloma formation with foreign body giant cell (FBGC) infiltration, and this is the main reason for graft failure. Diacylglycerol kinase (DAGK) is an important intracellular mediator of FBGC formation in macrophages. In this study, 4-hexylresorcinol (4HR) inhibited DAGKδ in a macrophage cell line (RAW264.7 cells). As a result of DAGK-δ inhibition by 4HR, FBGC formation was significantly inhibited in RAW264.7 cells. Silk fibroin is a well-known natural macromolecule, and when it is grafted into bone defects, it results in granuloma formation with massive FBGC formation. 4HR-incorporating silk graft materials displayed significant reduction of granuloma formation and increases in the extent of new bone formation in a rabbit calvarial defect model. In conclusion, 4HR could inhibit foreign body reaction via a DAGK-mediated pathway.
authors.affiliation: Department of Agricultural Biology, National Academy of Agricultural Science, RDA, Suwon 441-853, Republic of Korea.
authors.forename: HaeYong
authors.initials: H
authors.lastname: Kweon
authors.affiliation: Department of Oral and Maxillofacial Surgery, College of Dentistry, Gangneung-Wonju National University, Gangneung 210-702, Republic of Korea. Electronic address: kimsg@gwnu.ac.kr.
authors.forename: Seong-Gon
authors.initials: SG
authors.lastname: Kim
authors.affiliation: Department of Biochemistry and Cell Biology, BK21 Plus KNU Biomedical Convergence Program, Department of Biomedical Science, Skeletal Diseases Genome Research Center, School of Medicine, Kyungpook National University, Daegu 700-842, Republic of Korea.
authors.forename: Je-Yong
authors.initials: JY
authors.lastname: Choi
mesh_terms: D000818:Animals; D002114:Calcinosis / Q000473:pathology; D002130:Calcium Phosphates / Q000494:pharmacology; D002460:Cell Line; D019852:Diacylglycerol Kinase / Q000235:genetics*; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D005549:Foreign-Body Reaction / Q000188:drug therapy / Q000473:pathology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D015743:Giant Cells, Foreign-Body / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology*; D006604:Hexylresorcinol / Q000494:pharmacology* / Q000627:therapeutic use; D015847:Interleukin-4 / Q000494:pharmacology; D051379:Mice; D010712:Phosphatidic Acids / Q000378:metabolism; D011817:Rabbits; D047011:Silk / Q000494:pharmacology; D017550:Spectroscopy, Fourier Transform Infrared; D055114:X-Ray Microtomography
chemical_list: D002130:Calcium Phosphates; D004791:Enzyme Inhibitors; D010712:Phosphatidic Acids; D047011:Silk; C485817:beta-tricalcium phosphate; D015847:Interleukin-4; D019852:Diacylglycerol Kinase; D006604:Hexylresorcinol
keywords: Degradation; Foreign body giant cell; Foreign body response; Macrophage; Silk