title: Phospholipase Cγ1 suppresses foreign body giant cell formation by maintaining RUNX1 expression in macrophages.
abstract: Foreign body giant cell (FBGC) formation is associated with the inflammatory response following material implantation. However, the intracellular signaling events that regulate the process remain unclear. Here, we investigated the potential role of phospholipase C (PLC)γ1, a crucial enzyme required for growth factor-induced signaling, on FBGC formation. Knock-down of PLCγ1 using shRNA induced FBGC formation accompanied by increased expression of cathepsin K, DC-STAMP and CD36. Re-addition of PLCγ1 decreased FBGC formation. PLCγ1-deficiency caused a decrease in RUNX1 and subsequent PU.1 upregulation while subsequent rescue of RUNX1 in sh-PLCγ1-transfected cells strongly inhibited FBGC formation. FBGC generated by knock-down of PLCγ1 using shRNA resulted in strongly increased TNF-α production, with augmented activation of ERK, p38 MAPK and JNK, and subsequently NF-κB. Taken together, we suggest that PLCγ1 plays a role in the foreign body response by regulating the RUNX1/PU.1/DC-STAMP axis in macrophages.
authors.affiliation: Department of Biological Sciences, Sungkyunkwan University, Suwon, 16419, Republic of Korea.
authors.forename: Ye Seon
authors.initials: YS
authors.lastname: Kim
authors.affiliation: Department of Biological Sciences, Sungkyunkwan University, Suwon, 16419, Republic of Korea.
authors.forename: Chang Youp
authors.initials: CY
authors.lastname: Ok
authors.affiliation: Department of Hematology-Oncology, Ajou University School of Medicine, Suwon, 16499, Republic of Korea.
authors.forename: Joon Seong
authors.initials: JS
authors.lastname: Park
authors.affiliation: Department of Biological Sciences, Sungkyunkwan University, Suwon, 16419, Republic of Korea. Electronic address: hayoung@skku.edu.
authors.forename: Ha Young
authors.initials: HY
authors.lastname: Lee
authors.affiliation: Department of Biological Sciences, Sungkyunkwan University, Suwon, 16419, Republic of Korea; Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, 06351, Republic of Korea. Electronic address: yoesik@skku.edu.
authors.forename: Yoe-Sik
authors.initials: YS
authors.lastname: Bae
mesh_terms: D000818:Animals; D018955:CD36 Antigens / Q000235:genetics / Q000378:metabolism; D056657:Cathepsin K / Q000235:genetics / Q000378:metabolism; D002459:Cell Fusion; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D055785:Gene Knockdown Techniques; D015743:Giant Cells, Foreign-Body / Q000166:cytology* / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D008264:Macrophages / Q000166:cytology* / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism; D051966:Phospholipase C gamma / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D000067996:RAW 264.7 Cells; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation; D000099232:Proto-Oncogene Protein Spi-1
chemical_list: D018955:CD36 Antigens; D056657:Cathepsin K; D050676:Core Binding Factor Alpha 2 Subunit; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D051966:Phospholipase C gamma; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D000099232:Proto-Oncogene Protein Spi-1; C548810:CD36 protein (93-110); C499636:DC-STAMP protein, mouse; C493726:Runx1 protein, mouse
keywords: Foreign body giant cell; Fusogenic gene; Phospholipase Cγ1; RUNX1