PMID- 11001921 OWN - NLM STAT- MEDLINE DCOM- 20001025 LR - 20231213 IS - 0006-4971 (Print) IS - 0006-4971 (Linking) VI - 96 IP - 7 DP - 2000 Oct 1 TI - Maturation of dendritic cells leads to up-regulation of cellular FLICE-inhibitory protein and concomitant down-regulation of death ligand-mediated apoptosis. PG - 2628-31 AB - Dendritic cells (DCs) disappear from lymph nodes 1 to 2 days after antigen presentation, presumably by apoptosis. To evaluate the role of death ligands in elimination of DCs, we analyzed the sensitivity of human DCs to CD95 ligand (CD95L) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). We found mature DCs to be resistant to killing via CD95L or TRAIL, whereas only immature DCs were partially sensitive. However, all DC populations expressed CD95, TRAIL-R2, and TRAIL-R3 at comparable levels, suggesting that sensitivity to death ligand-induced DC apoptosis is not regulated at the receptor level. Interestingly, mature DCs highly expressed the caspase 8 inhibitory protein cFLIP, whereas only low levels were detected in immature DCs. Thus, death ligand sensitivity proved to be dependent on DC maturation and inversely correlated with expression levels of cFLIP. Induction of apoptosis by TRAIL or CD95L does not seem to play a role in the elimination of mature DCs, but instead might serve to regulate immature DC populations. FAU - Leverkus, M AU - Leverkus M AD - University of Wurzburg Medical School, Department of Dermatology, Wurzburg, Germany. FAU - Walczak, H AU - Walczak H FAU - McLellan, A AU - McLellan A FAU - Fries, H W AU - Fries HW FAU - Terbeck, G AU - Terbeck G FAU - Brocker, E B AU - Brocker EB FAU - Kampgen, E AU - Kampgen E LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Blood JT - Blood JID - 7603509 RN - 0 (Antigens, CD) RN - 0 (Apoptosis Regulatory Proteins) RN - 0 (Immunoglobulins) RN - 0 (Interleukin-1) RN - 0 (Interleukin-6) RN - 0 (Membrane Glycoproteins) RN - 0 (TNF-Related Apoptosis-Inducing Ligand) RN - 0 (TNFSF10 protein, human) RN - 0 (Tumor Necrosis Factor-alpha) RN - 0 (fas Receptor) RN - 207137-56-2 (Interleukin-4) RN - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor) RN - EC 3.4.22.- (CASP8 protein, human) RN - EC 3.4.22.- (CASP9 protein, human) RN - EC 3.4.22.- (Caspase 8) RN - EC 3.4.22.- (Caspase 9) RN - EC 3.4.22.- (Caspases) RN - K7Q1JQR04M (Dinoprostone) SB - IM MH - Antigens, CD MH - *Apoptosis MH - Apoptosis Regulatory Proteins MH - Caspase 8 MH - Caspase 9 MH - Caspases/metabolism MH - Cells, Cultured MH - Dendritic Cells/chemistry/*physiology MH - Dinoprostone/pharmacology MH - Drug Resistance MH - Granulocyte-Macrophage Colony-Stimulating Factor/pharmacology MH - Humans MH - Immunoglobulins/analysis MH - Interleukin-1/pharmacology MH - Interleukin-4/pharmacology MH - Interleukin-6/pharmacology MH - Membrane Glycoproteins/analysis/*pharmacology MH - TNF-Related Apoptosis-Inducing Ligand MH - Tumor Necrosis Factor-alpha/analysis/*pharmacology MH - fas Receptor/analysis/*pharmacology MH - CD83 Antigen EDAT- 2000/09/26 11:00 MHDA- 2001/02/28 10:01 CRDT- 2000/09/26 11:00 PHST- 2000/09/26 11:00 [pubmed] PHST- 2001/02/28 10:01 [medline] PHST- 2000/09/26 11:00 [entrez] AID - S0006-4971(20)54378-4 [pii] PST - ppublish SO - Blood. 2000 Oct 1;96(7):2628-31.