PMID- 15710334
OWN - NLM
STAT- MEDLINE
DCOM- 20050727
LR  - 20131121
IS  - 1567-5769 (Print)
IS  - 1567-5769 (Linking)
VI  - 5
IP  - 4
DP  - 2005 Apr
TI  - Biochemical effects of KH 1060 and anti-TNF monoclonal antibody on human 
      peripheral blood mononuclear cells.
PG  - 649-59
AB  - The aim of this study was to investigate whether the vitamin D analogue KH 1060 
      could exert a suppressive action on Tumor necrosis factor-alpha (TNF-alpha). The 
      chimeric anti-TNF-alpha monoclonal antibody (anti-TNF), alone or in combination 
      with KH 1060, was also used. KH 1060 (0.01, 0.1, 1 nM) significantly inhibited 
      cell proliferation, determined after 5 days by [3H]thymidine incorporation, when 
      peripheral blood mononuclear cells (PBMC), obtained from healthy subjects, were 
      stimulated with phytohaemagglutinin (PHA) and incubated for 24 h in the absence 
      and in the presence of lipopolysaccharide (LPS). In the same experimental 
      conditions, anti-TNF exerted a significant inhibition on PBMC proliferation, at 
      the lowest doses (0.001, 0.01 microg/ml) in the absence of LPS, and at 0.001, 1, 
      10 microg/ml in its presence. A synergistic inhibition was registered combining 
      KH 1060 and anti-TNF, at well-defined concentrations. 0.1 nM KH 1060 produced a 
      significant decrease in TNF-alpha levels, determined by ELISA, although less 
      remarkable than in the presence of anti-TNF. This decrease was synergistic, 
      associating 0.1 nM KH 1060 and 0.1 microg/ml anti-TNF. VDR protein levels were 
      increased by 0.1 nM KH 1060, 0.1 microg/ml anti-TNF or their combination. The 
      protein levels of two oncogenes, Bax and Bcl-2, remained unchanged, when PBMC 
      were incubated with KH 1060, anti-TNF or their combination in the absence of LPS, 
      while, in its presence, an increase was registered. The demonstrated 
      anti-TNF-alpha effect of KH 1060 may suggest for this compound an 
      immunosuppressive action and the possibility to synergistically act with other 
      drugs.
FAU - Stio, Maria
AU  - Stio M
AD  - Department of Biochemical Sciences, University of Florence, Viale Morgagni 50, 
      I-50134 Florence, Italy. maria.stio@unifi.it
FAU - Treves, Cristina
AU  - Treves C
FAU - Martinesi, Maria
AU  - Martinesi M
FAU - Bonanomi, Andrea G
AU  - Bonanomi AG
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - Int Immunopharmacol
JT  - International immunopharmacology
JID - 100965259
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (BAX protein, human)
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (Receptors, Calcitriol)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (bcl-2-Associated X Protein)
RN  - 131875-08-6 (KH 1060)
RN  - FXC9231JVH (Calcitriol)
SB  - IM
MH  - Antibodies, Monoclonal/immunology/*pharmacology
MH  - Calcitriol/*analogs & derivatives/*pharmacology
MH  - Cell Proliferation/drug effects
MH  - Gene Expression/drug effects
MH  - Genes, bcl-2/physiology
MH  - Humans
MH  - Immunosuppressive Agents/*pharmacology
MH  - Leukocytes, Mononuclear/*drug effects
MH  - Lipopolysaccharides/pharmacology
MH  - Proto-Oncogene Proteins c-bcl-2/metabolism
MH  - Receptors, Calcitriol/metabolism
MH  - Tumor Necrosis Factor-alpha/*antagonists & inhibitors/immunology
MH  - bcl-2-Associated X Protein
EDAT- 2005/02/16 09:00
MHDA- 2005/07/28 09:00
CRDT- 2005/02/16 09:00
PHST- 2004/11/03 00:00 [received]
PHST- 2004/11/03 00:00 [accepted]
PHST- 2005/02/16 09:00 [pubmed]
PHST- 2005/07/28 09:00 [medline]
PHST- 2005/02/16 09:00 [entrez]
AID - S1567-5769(04)00360-1 [pii]
AID - 10.1016/j.intimp.2004.11.002 [doi]
PST - ppublish
SO  - Int Immunopharmacol. 2005 Apr;5(4):649-59. doi: 10.1016/j.intimp.2004.11.002.