PMID- 15949143 OWN - NLM STAT- MEDLINE DCOM- 20050823 LR - 20240109 IS - 0968-0519 (Print) IS - 0968-0519 (Linking) VI - 11 IP - 3 DP - 2005 TI - Differential maturation of murine bone-marrow derived dendritic cells with lipopolysaccharide and tumor necrosis factor-alpha. PG - 145-60 AB - 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-alpha (TNF-alpha), 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-alpha exposure produced a phenotypically distinct DC. Gene expression patterns in DCs 6 and 24 h after LPS and TNF-alpha 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-alpha 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. FAU - Efron, Philip A AU - Efron PA AD - Department of Surgery, University of Florida College of Medicine, Gainesville, 32610, USA. FAU - Tsujimoto, Hironori AU - Tsujimoto H FAU - Bahjat, Frances R AU - Bahjat FR FAU - Ungaro, Ricardo AU - Ungaro R FAU - Debernardis, Justin AU - Debernardis J FAU - Tannahill, Cynthia AU - Tannahill C FAU - Baker, Henry V AU - Baker HV FAU - Edwards, Carl K AU - Edwards CK FAU - Moldawer, Lyle L AU - Moldawer LL LA - eng GR - R01 GM63041-03/GM/NIGMS NIH HHS/United States GR - R37 GM-40561-15/GM/NIGMS NIH HHS/United States GR - T32 GM-08721-04/GM/NIGMS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - J Endotoxin Res JT - Journal of endotoxin research JID - 9433350 RN - 0 (Antigens) RN - 0 (Lipopolysaccharides) RN - 0 (Tumor Necrosis Factor-alpha) SB - IM MH - Animals MH - Antigens MH - Bone Marrow Cells MH - *Cell Differentiation MH - Dendritic Cells/*physiology MH - Female MH - *Gene Expression Profiling MH - Humans MH - Inflammation MH - Lipopolysaccharides/*pharmacology MH - Mice MH - Mice, Inbred C57BL MH - Phenotype MH - Tumor Necrosis Factor-alpha/*physiology EDAT- 2005/06/14 09:00 MHDA- 2005/08/24 09:00 CRDT- 2005/06/14 09:00 PHST- 2005/06/14 09:00 [pubmed] PHST- 2005/08/24 09:00 [medline] PHST- 2005/06/14 09:00 [entrez] AID - 10.1179/096805105X46583 [doi] PST - ppublish SO - J Endotoxin Res. 2005;11(3):145-60. doi: 10.1179/096805105X46583.