PMID- 9491782
OWN - NLM
STAT- MEDLINE
DCOM- 19980312
LR  - 20181201
IS  - 0021-9541 (Print)
IS  - 0021-9541 (Linking)
VI  - 175
IP  - 1
DP  - 1998 Apr
TI  - RAR-, not RXR, ligands inhibit cell activation and prevent apoptosis in 
      B-lymphocytes.
PG  - 68-77
AB  - We have previously shown that retinoids inhibit activation of human peripheral 
      blood B-lymphocytes. In the present paper, we wished to explore the involvement 
      of nuclear retinoid-specific receptors in this process by using ligands specific 
      for the retinoic acid receptors (RARs) and retinoid X receptors (RXRs). We found 
      that the RAR-specific ligand TTAB reduced anti-IgM-induced B-cell activation in a 
      dose-dependent manner. Thus, at 100 nM of TTAB, DNA synthesis was reduced by 
      approximately 60%. In contrast, the RXR-selective ligand SR11217 had no effect on 
      DNA synthesis. Similar findings were obtained when the expression of the 
      activation antigen CD71 (appears late in G1) was examined. The role of retinoids 
      in apoptosis of resting peripheral blood B-lymphocytes was examined using the 
      same receptor-selective ligands. Again, we found that the RAR-selective ligands 
      were more potent effectors than were the RXR-selective ligands. In spite of the 
      inhibitory effects of retinoids on B-cell proliferation, the same retinoids 
      significantly promoted the survival of the cells. Thus, 10 nM TTAB significantly 
      reduced spontaneous apoptosis of in vitro cultured B-cells at day 3 from 45% to 
      30%, as determined by vital dye staining and DNA end-labeling. Again, the 
      RXR-specific ligand SR11217 had no effect. Interestingly, we found that CD40 
      ligand was able to potentiate the retinoid-mediated inhibition of apoptosis. By 
      reverse transcriptase polymerase chain reaction (PCR), we found that peripheral 
      blood B-lymphocytes expressed RARalpha, RARgamma, and RXRalpha, but not RARbeta, 
      RXRbeta, or RXRgamma. Hence, the lack of effect of the RXR-specific ligand 
      SR11217 on growth and apoptosis was not due to absence of RXRs. In conclusion, 
      the ability of retinoids to inhibit growth and prevent apoptosis of normal human 
      B-lymphocytes indicates a dual role of retinoids in this cell compartment, and it 
      appears that both effects of retinoids are mediated via RARs and not RXRs.
FAU - Lomo, J
AU  - Lomo J
AD  - Department of Immunology, Institute for Cancer Research, The Norwegian Radium 
      Hospital, Montebello, Oslo.
FAU - Smeland, E B
AU  - Smeland EB
FAU - Ulven, S
AU  - Ulven S
FAU - Natarajan, V
AU  - Natarajan V
FAU - Blomhoff, R
AU  - Blomhoff R
FAU - Gandhi, U
AU  - Gandhi U
FAU - Dawson, M I
AU  - Dawson MI
FAU - Blomhoff, H K
AU  - Blomhoff HK
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Cell Physiol
JT  - Journal of cellular physiology
JID - 0050222
RN  - 0 (CD40 Antigens)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Immunoglobulin M)
RN  - 0 (Ligands)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Receptors, Retinoic Acid)
RN  - 0 (Retinoid X Receptors)
RN  - 0 (Retinoids)
RN  - 0 (Transcription Factors)
RN  - 107430-51-3 (4-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-anthracenyl)benzoic 
      acid)
RN  - 146670-35-1 (SR 11217)
RN  - 147205-72-9 (CD40 Ligand)
RN  - 1UA8E65KDZ (Alitretinoin)
RN  - 207137-56-2 (Interleukin-4)
RN  - 5688UTC01R (Tretinoin)
RN  - 9007-49-2 (DNA)
SB  - IM
MH  - Alitretinoin
MH  - Apoptosis/*drug effects/immunology
MH  - B-Lymphocytes/*chemistry/*cytology/immunology
MH  - CD40 Antigens/pharmacology
MH  - CD40 Ligand
MH  - DNA/biosynthesis
MH  - DNA-Binding Proteins/genetics/immunology
MH  - Gene Expression/drug effects/immunology
MH  - Humans
MH  - Immunoglobulin M/immunology
MH  - Interleukin-4/pharmacology
MH  - Ligands
MH  - Lymphocyte Activation/drug effects
MH  - Membrane Glycoproteins/pharmacology
MH  - Receptors, Retinoic Acid/genetics/*immunology
MH  - Retinoid X Receptors
MH  - Retinoids/pharmacology
MH  - Transcription Factors/genetics/*immunology
MH  - Transcription, Genetic/drug effects/immunology
MH  - Transfection
MH  - Tretinoin/pharmacology
EDAT- 1998/03/10 03:04
MHDA- 2000/06/20 09:00
CRDT- 1998/03/10 03:04
PHST- 1998/03/10 03:04 [pubmed]
PHST- 2000/06/20 09:00 [medline]
PHST- 1998/03/10 03:04 [entrez]
AID - 10.1002/(SICI)1097-4652(199804)175:1<68::AID-JCP8>3.0.CO;2-A [pii]
AID - 10.1002/(SICI)1097-4652(199804)175:1<68::AID-JCP8>3.0.CO;2-A [doi]
PST - ppublish
SO  - J Cell Physiol. 1998 Apr;175(1):68-77. doi: 
      10.1002/(SICI)1097-4652(199804)175:1<68::AID-JCP8>3.0.CO;2-A.