title: Reverse signaling from LIGHT promotes pro-inflammatory responses in the human monocytic leukemia cell line, THP-1.
abstract: LIGHT is a type II transmembrane protein belonging to the TNF superfamily which is involved in co-stimulation of T cells or apoptosis in tumors. In this study, the possibility of LIGHT-mediated reverse signaling was tested in the human monocytic leukemia cell line, THP-1. For stimulation of LIGHT, cells were stimulated with specific monoclonal antibody and changes in macrophage-related functions such as phagocytosis, adhesion, migration, cytokine secretion, and production of pro-inflammatory mediators were tested. Triggering of LIGHT induced production of pro-inflammatory mediators such as interleukin (IL)-8 and matrix metalloproteinase (MMP)-9 while suppressing the phagocytic activity. Utilization of signaling inhibitors and Western blot demonstrated that LIGHT activated ERK MAPK and PI3K and the major inflammatory transcription factor NF-κB. These data indicate that LIGHT-mediated signaling could modulate the macrophage activities and that successful regulation of its activity could be beneficial to the treatment of chronic inflammatory conditions where macrophages play an important role.
authors.affiliation: School of Life Sciences and Biotechnology, Kyungpook National University, Daegu 702-701, Republic of Korea.
authors.forename: Su-Geun
authors.initials: SG
authors.lastname: Lim
authors.forename: Kyoungho
authors.initials: K
authors.lastname: Suk
authors.forename: Won-Ha
authors.initials: WH
authors.lastname: Lee
mesh_terms: D002448:Cell Adhesion / Q000276:immunology; D045744:Cell Line, Tumor; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000276:immunology*; D018836:Inflammation Mediators / Q000276:immunology; D016209:Interleukin-8 / Q000096:biosynthesis; D008264:Macrophages / Q000276:immunology*; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D016328:NF-kappa B / Q000378:metabolism; D010587:Phagocytosis; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D015398:Signal Transduction; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14 / Q000378:metabolism*; D015054:Zymosan / Q000378:metabolism
chemical_list: D018836:Inflammation Mediators; D016209:Interleukin-8; D016328:NF-kappa B; C505914:TNFSF14 protein, human; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14; D015054:Zymosan; D019869:Phosphatidylinositol 3-Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D020780:Matrix Metalloproteinase 9
keywords: IL-8; Inflammation; LIGHT; MMP-9; Macrophage; Reverse signaling