PMID- 19301111
OWN - NLM
STAT- MEDLINE
DCOM- 20090901
LR  - 20211020
IS  - 1573-2576 (Electronic)
IS  - 0360-3997 (Linking)
VI  - 32
IP  - 3
DP  - 2009 Jun
TI  - Etanercept impairs maturation of human monocyte-derived dendritic cells by 
      inhibiting the autocrine TNFalpha-mediated signaling.
PG  - 146-50
LID - 10.1007/s10753-009-9113-7 [doi]
AB  - The success of anti-tumor necrosis factor alpha (TNFalpha) therapies has led to 
      increased interest as to the mechanisms and consequences of TNFalpha blockade. 
      The aim of the study was to examine the effects of TNFalpha blockade by 
      etanercept on lipopolysaccharide (LPS) or peptidoglycan (PG)-induced maturation 
      of human monocyte-derived dendritic cells (MDDCs). MDDCs grown from peripheral 
      blood of healthy donors were stimulated by LPS or PG with/without the presence of 
      etanercept. Concentrations of TNFalpha in cell supernatants were assessed by 
      ELISA, while the cells were stained with monoclonal antibodies to CD83, CD80, 
      CD86, CD11c, CD40, HLA-DR, and annexin-V and acquired using a flow cytometer. 
      Etanercept significantly decreased the stimulated cell surface expression of 
      HLA-DR, CD80, CD86, CD40 and CD83 on MDDCs in all examined samples. Etanercept in 
      the same dose, but denatured to loss of specificity for TNFalpha, failed to 
      change any of the aforementioned markers. In the presence of etanercept, 
      concentrations of TNFalpha in cell supernatants were decreased by 53% on average, 
      with a range of 25%-87%. Etanercept impaired the stimulated maturation of MDDCs 
      by neutralizing the induced TNFalpha, produced by the same MDDCs after antigenic 
      stimulation. The reported data confirms that TNFalpha blockade may have a direct 
      effect on DCs, with a wide spectrum of potential secondary effects downstream. 
      The data also suggests the presence of TNFalpha-mediated autocrine signaling, 
      serving to accelerate or catalyze the maturation process of MDDCs.
FAU - Slobodin, Gleb
AU  - Slobodin G
AD  - Department of Internal Medicine A, Bnai Zion Medical Center, Ruth and Bruce 
      Rappaport Faculty of Medicine, Technion, Haifa, Israel. gslobodin@yahoo.com
FAU - Kessel, Aharon
AU  - Kessel A
FAU - Peri, Regina
AU  - Peri R
FAU - Zaigraikin, Natalia
AU  - Zaigraikin N
FAU - Rozenbaum, Michael
AU  - Rozenbaum M
FAU - Rosner, Itzhak
AU  - Rosner I
FAU - Toubi, Elias
AU  - Toubi E
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Inflammation
JT  - Inflammation
JID - 7600105
RN  - 0 (Antigens, Surface)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Immunologic Factors)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Peptidoglycan)
RN  - 0 (Receptors, Tumor Necrosis Factor)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - OP401G7OJC (Etanercept)
SB  - IM
MH  - Antigens, Surface/analysis
MH  - Autocrine Communication/drug effects
MH  - Cells, Cultured
MH  - Dendritic Cells/*drug effects
MH  - Etanercept
MH  - Humans
MH  - Immunoglobulin G/*pharmacology
MH  - Immunologic Factors
MH  - Lipopolysaccharides/pharmacology
MH  - Monocytes/cytology
MH  - Peptidoglycan/pharmacology
MH  - Receptors, Tumor Necrosis Factor
MH  - Signal Transduction/*drug effects
MH  - Tumor Necrosis Factor-alpha/analysis/*antagonists & inhibitors/metabolism
EDAT- 2009/03/21 09:00
MHDA- 2009/09/02 06:00
CRDT- 2009/03/21 09:00
PHST- 2009/03/21 09:00 [entrez]
PHST- 2009/03/21 09:00 [pubmed]
PHST- 2009/09/02 06:00 [medline]
AID - 10.1007/s10753-009-9113-7 [doi]
PST - ppublish
SO  - Inflammation. 2009 Jun;32(3):146-50. doi: 10.1007/s10753-009-9113-7.