Journal
IMMUNOLOGY LETTERS
Volume 136, Issue 1, Pages 97-107Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.imlet.2011.01.001
Keywords
ATRA; Human TLR-5; Flagellin; NF-kappa B; Allostimulatory capacity; THP-1 cells
Categories
Funding
- Korea government (MOST) [R13-2007-023-00000-0]
- Inje University
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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-kappa B and the RAR alpha 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-alpha, 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. (C) 2011 Elsevier B.V. All rights reserved.
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