PMID- 18414382
OWN - NLM
STAT- MEDLINE
DCOM- 20080731
LR  - 20211020
IS  - 0007-1188 (Print)
IS  - 1476-5381 (Electronic)
IS  - 0007-1188 (Linking)
VI  - 154
IP  - 3
DP  - 2008 Jun
TI  - AM3, a natural glycoconjugate, induces the functional maturation of human 
      dendritic cells.
PG  - 698-708
LID - 10.1038/bjp.2008.87 [doi]
AB  - BACKGROUND AND PURPOSE: Dendritic cells (DCs) are dedicated antigen-presenting 
      cells able to initiate specific immune responses and their maturation is critical 
      for the induction of antigen-specific T-lymphocyte responses. Here, we have 
      investigated the effects of Inmunoferon-active principle (AM3), the active agent 
      of a commercial immunomodulatory drug, on human monocyte-derived DCs (MDDCs). 
      EXPERIMENTAL APPROACH: MDDCs derived from healthy and hepatitis C virus 
      (HCV)-infected patients were stimulated with AM3. We analysed the expression of 
      cell surface proteins by flow cytometry, that of cytokine production by ELISA, 
      and the expression of chemokines and chemokine receptors by RNase protection 
      assays. T-lymphocyte proliferation was assessed in mixed lymphocyte reactions, 
      protein expression by western blot and luciferase-based reporter methods, and 
      Toll-like receptor (TLR)-blocking antibodies were employed to analyse TLR 
      activity. KEY RESULTS: In MDDCs, AM3 induced or enhanced expression of CD54, 
      CD83, CD86, HLA-DR, chemokines and chemokine receptors, interleukin (IL)-12p70 
      and IL-10. Furthermore, AM3 stimulated MDDCs to increase proliferation of 
      allogenic T cells. AM3 triggered nuclear translocation of NF-kappaB and 
      phosphorylation of p38 mitogen-activated protein kinase. AM3 promoted NF-kappaB 
      activation in a TLR-4-dependent manner, and blocking TLR-4 activity attenuated 
      the enhanced expression of CD80, CD83 and CD86 induced by AM3. AM3 enhanced the 
      expression of maturation-associated markers in MDDCs from HCV-infected patients 
      and increased the proliferation of T lymphocytes induced by these MDDCs. 
      CONCLUSIONS AND IMPLICATIONS: These results underline the effects of AM3 in 
      promoting maturation of MDDCs and suggest that AM3 might be useful in regulating 
      immune responses in pathophysiological situations requiring DC maturation.
FAU - Martin-Vilchez, S
AU  - Martin-Vilchez S
AD  - Liver Unit, Hospital Universitario de la Princesa, CIBER-EHD, Spain.
FAU - Molina-Jimenez, F
AU  - Molina-Jimenez F
FAU - Alonso-Lebrero, J L
AU  - Alonso-Lebrero JL
FAU - Sanz-Cameno, P
AU  - Sanz-Cameno P
FAU - Rodriguez-Munoz, Y
AU  - Rodriguez-Munoz Y
FAU - Benedicto, I
AU  - Benedicto I
FAU - Roda-Navarro, P
AU  - Roda-Navarro P
FAU - Trapero, M
AU  - Trapero M
FAU - Aragoneses-Fenoll, L
AU  - Aragoneses-Fenoll L
FAU - Gonzalez, S
AU  - Gonzalez S
FAU - Pivel, J P
AU  - Pivel JP
FAU - Corbi, A L
AU  - Corbi AL
FAU - Lopez-Cabrera, M
AU  - Lopez-Cabrera M
FAU - Moreno-Otero, R
AU  - Moreno-Otero R
FAU - Majano, P L
AU  - Majano PL
LA  - eng
PT  - Journal Article
DEP - 20080414
PL  - England
TA  - Br J Pharmacol
JT  - British journal of pharmacology
JID - 7502536
RN  - 0 (Adjuvants, Immunologic)
RN  - 0 (Calcium Phosphates)
RN  - 0 (Chemokines)
RN  - 0 (Glycopeptides)
RN  - 0 (Receptors, Chemokine)
RN  - 0 (Toll-Like Receptor 4)
RN  - 87139-86-4 (Immunoferon)
SB  - IM
MH  - Adjuvants, Immunologic/*pharmacology
MH  - Aged
MH  - Blotting, Western
MH  - Calcium Phosphates/*pharmacology
MH  - Cell Proliferation/drug effects
MH  - Chemokines/drug effects/metabolism
MH  - Dendritic Cells/*drug effects/metabolism
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Flow Cytometry
MH  - Gene Expression Regulation/drug effects
MH  - Glycopeptides/*pharmacology
MH  - Hepatitis C/metabolism
MH  - Humans
MH  - Middle Aged
MH  - Receptors, Chemokine/drug effects/metabolism
MH  - T-Lymphocytes/drug effects/metabolism
MH  - Toll-Like Receptor 4/drug effects/metabolism
PMC - PMC2439514
EDAT- 2008/04/17 09:00
MHDA- 2008/08/01 09:00
PMCR- 2008/06/01
CRDT- 2008/04/17 09:00
PHST- 2008/04/17 09:00 [pubmed]
PHST- 2008/08/01 09:00 [medline]
PHST- 2008/04/17 09:00 [entrez]
PHST- 2008/06/01 00:00 [pmc-release]
AID - bjp200887 [pii]
AID - 10.1038/bjp.2008.87 [doi]
PST - ppublish
SO  - Br J Pharmacol. 2008 Jun;154(3):698-708. doi: 10.1038/bjp.2008.87. Epub 2008 Apr 
      14.