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Differential maturation of murine bone-marrow derived dendritic cells with lipopolysaccharide and tumor necrosis factor-

Department of Surgery, University of Florida College of Medicine, Gainesville, Florida, USA

Hironori Tsujimoto

Department of Surgery, University of Florida College of Medicine, Gainesville, Florida, USA

Frances R. Bahjat

Department of Surgery, University of Florida College of Medicine, Gainesville, Florida, USA

Ricardo Ungaro

Department of Surgery, University of Florida College of Medicine, Gainesville, Florida, USA

Justin Debernardis

Department of Surgery, University of Florida College of Medicine, Gainesville, Florida, USA

Cynthia Tannahill

Department of Surgery, University of Florida College of Medicine, Gainesville, Florida, USA

Henry V. Baker

Department of Molecular Genetics and Microbiology, University of Florida College of Medicine, Gainesville, Florida, USA

Carl K. Edwards

Division of Inflammation, Amgen Inc., Thousand Oaks, California, USA

Lyle L. Moldawer

Department of Surgery, University of Florida College of Medicine, Gainesville, Florida, USA, moldawer{at}surgery.ufl.edu

Dendritic cells (DCs) play a key role in the interface between the innate and acquired immune systems. In response to both exogenous as well as endogenous signals, DCs undergo a programmed maturation to become an efficient, antigen-presenting cell. Yet little is known regarding the differential responses by endogenous versus exogenous stimuli on DC maturation. In the present report, we have compared the phenotypic, functional, and genome-wide expression responses associated with maturation by bone marrow derived DCs to either an endogenous danger signal, tumor necrosis factor- (TNF-), or a microbial product, bacterial lipopolysaccharide (LPS). Examination of the cell surface expression of DCs as well as cytokine production demonstrated that patterns of DC maturation varied dramatically depending upon the stimulus. Whereas LPS was highly effective in terms of inducing phenotypic and functional maturation, TNF- exposure produced a phenotypically distinct DC. Gene expression patterns in DCs 6 and 24 h after LPS and TNF- exposure revealed that these activation signals produce fundamentally different genomic responses. Supervised analysis revealed that the expression of 929 probe sets discriminated among the treatment groups, and the patterns of gene expression in TNF- stimulated DCs were more similar to unstimulated cells at both 6 and 24 h post-stimulation than to LPS-stimulated cells at the same time points. These findings reveal that DCs are capable of a varying phenotypic response to different antigens and endogenous signals.

Key Words: Inflammation • gene expression analysis • cytokines

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