title: All-trans retinoic acid induces TLR-5 expression and cell differentiation and promotes flagellin-mediated cell functions in human THP-1 cells.
abstract: Toll-like receptor 5 (TLR-5), which is expressed on macrophages and dendritic cells (DCs), is a crucial cell surface molecule that senses microbial-associated molecular patterns and initiates host innate immune responses upon infection with invaders that express flagellin. Little information is known about the induction factors and mechanisms of TLR-5 expression. In this study, we demonstrate that all-trans retinoic acid (ATRA) significantly up-regulated TLR-5 expression in human macrophage THP-1 cells by co-activating NF-κB and the RARα receptor and inducing the differentiation of CD11b(-)CD11c(-) THP-1 cells to CD11b(+)CD11c(low) cells. Furthermore, when stimulated with flagellin, ATRA-induced THP-1 cells expressed multiple cytokines, including TNF-α, IL-1beta, and IL-12p40, and several co-stimulatory molecules, such as CD40, CD80, CD86, and MHC class I and II. We also showed that when ATRA-induced THP-1 cells were stimulated with flagellin, the cells displayed an allostimulatory capacity rather than phagocytic activity. Taken together, our findings suggest that ATRA is a crucial immunostimulatory cofactor that induces the activation of macrophages and their subsequent differentiation into dendritic-like cells.
authors.affiliation: Advanced Research Center for Multiple Myeloma, Department of Microbiology, College of Medicine, Inje University, Busan 614-735, Republic of Korea.
authors.forename: Hae-Yun
authors.initials: HY
authors.lastname: Cho
authors.forename: Eun-Kyoung
authors.initials: EK
authors.lastname: Choi
authors.forename: Soo-Woon
authors.initials: SW
authors.lastname: Lee
authors.forename: Ki-Hyung
authors.initials: KH
authors.lastname: Kim
authors.forename: Sang-Jun
authors.initials: SJ
authors.lastname: Park
authors.forename: Chae Kwan
authors.initials: CK
authors.lastname: Lee
authors.forename: Soo-Woong
authors.initials: SW
authors.lastname: Lee
mesh_terms: D002454:Cell Differentiation; D002460:Cell Line; D005408:Flagellin / Q000276:immunology*; D005786:Gene Expression Regulation; D006801:Humans; D016328:NF-kappa B / Q000276:immunology / Q000378:metabolism; D011401:Promoter Regions, Genetic; D018168:Receptors, Retinoic Acid / Q000276:immunology; D000072482:Retinoic Acid Receptor alpha; D012486:Salmonella typhimurium / Q000276:immunology*; D015398:Signal Transduction; D051198:Toll-Like Receptor 5 / Q000235:genetics / Q000276:immunology*; D014212:Tretinoin / Q000276:immunology*
chemical_list: D016328:NF-kappa B; C000607071:RARA protein, human; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; C495346:TLR5 protein, human; D051198:Toll-Like Receptor 5; D005408:Flagellin; D014212:Tretinoin