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Osteoprotegerin expression in dendritic cells increases with maturation and is NF‐κB‐dependent
Author(s) -
Schoppet Michael,
Henser Stephanie,
Ruppert Volker,
Stübig Thomas,
AlFakhri Nadia,
Maisch Bernhard,
Hofbauer Lorenz C.
Publication year - 2006
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.21129
Subject(s) - osteoprotegerin , microbiology and biotechnology , nf κb , expression (computer science) , chemistry , biology , computer science , signal transduction , receptor , biochemistry , programming language , activator (genetics)
Dendritic cells (DC) comprise a unique leukocyte population which controls primary immune responses. Recent studies indicate that DC express osteoprotegerin (OPG), a secreted tumor necrosis factor receptor homolog, which regulates DC survival, monocyte chemotaxis, and B cell development and function by ligating TNF family member receptor activator of NF‐κB ligand (RANKL). The precise regulators of OPG expression in DC have not been investigated. In this study, we assessed OPG mRNA steady state levels by Northern blot analysis and OPG protein secretion by an immunoassay in monocyte‐derived DC of different maturation, and the effect of different cytokines and hormones on OPG expression. OPG was upregulated with maturation of DC, whereas pretreatment of DC with 1α,25(OH) 2 vitamin D 3 , tamoxifen, or dexamethasone, agents that inhibit differentiation of DC, decreased OPG expression. In vivo, OPG was found to be colocalized with mature CD83 + DC in human tonsils by immunofluorescence confocal microscopy analysis. Furthermore, OPG was upregulated by TNF superfamily members TNF‐α, anti‐CD40, and RANKL, and by ligands of the Toll‐like/IL‐1 receptor family including IL‐1β, double‐stranded RNA (poly I:C), or lipopolysaccharide (LPS), all of which induce maturation of DC. Gene silencing by small interfering RNA (siRNA) directed against transcription factor NF‐κB abrogated the expression of OPG as demonstrated by real‐time PCR. In summary, we describe that the expression of OPG by DC increases with maturation and is NF‐κB‐dependent, possibly regulating immune responses in lymphoid tissues. J. Cell. Biochem. 100: 1430–1439, 2007. © 2006 Wiley‐Liss, Inc.