PMID- 11970994
OWN - NLM
STAT- MEDLINE
DCOM- 20020517
LR  - 20190515
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 168
IP  - 9
DP  - 2002 May 1
TI  - Vitamin A enhances in vitro Th2 development via retinoid X receptor pathway.
PG  - 4495-503
AB  - Vitamin A deficiency diminishes Th2-mediated Ab responses, and high-level dietary 
      vitamin A or treatment with the vitamin A metabolite retinoic acid (RA) enhances 
      such responses. To identify a potential mechanism(s) underlying this in vivo 
      activity of vitamin A, we examined the effects of all-trans and 9-cis RA on 
      development of Th1 and Th2 cell populations using in vitro stimulation of 
      Ag-naive Th0 cells from the DO11.10 TCR-transgenic mouse. Treatment with 9-cis, 
      but not with all-trans RA, at primary stimulation strongly enhanced Th2 
      development. IL-4-neutralizing Ab blocked this activity, but IL-12- and 
      IFN-gamma-neutralizing Ab did not. Because 9-cis RA regulates gene transcription 
      via either RA receptors or retinoid X receptors (RXRs), we tested the 
      Th2-enhancing activities of the RXR- and RA receptor-selective agonists AGN194204 
      and 
      4-((E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1-propenyl)benzoic 
      acid (TTNPB). AGN194204 strongly enhanced Th2 development, whereas TTNPB did not. 
      This RXR agonist also enhanced Th2 development when purified, naive Th0 cells 
      (L-selectin(high)/CD4(+)) were stimulated with CD3 and CD28 Abs in the absence of 
      APCs. During primary antigenic stimulation of naive Th0 cells from DO11.10 mice, 
      AGN194204 increased IL-4 and IL-5 production, decreased IFN-gamma production, 
      increased mRNA in responding T cells for genes involved in Th2 development (IL-4, 
      GATA-3, and c-maf), and decreased mRNA for genes involved in Th1 development 
      (IFN-gamma, T-bet, and IL-12R). These data show that stimulation of the RXR 
      pathway enhances Th2 development, perhaps by affecting the relative expression of 
      pertinent transcription factors, cytokines, and cytokine receptors.
FAU - Stephensen, Charles B
AU  - Stephensen CB
AD  - U.S. Department of Agriculture Western Human Nutrition Research Center and 
      Nutrition Department, University of California, Davis, CA 95616, USA. 
      cstephenson@ucdavis.edu
FAU - Rasooly, Reuven
AU  - Rasooly R
FAU - Jiang, Xiaowen
AU  - Jiang X
FAU - Ceddia, Michael A
AU  - Ceddia MA
FAU - Weaver, Casey T
AU  - Weaver CT
FAU - Chandraratna, Roshantha A S
AU  - Chandraratna RA
FAU - Bucy, R Patterson
AU  - Bucy RP
LA  - eng
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (AGN 194204)
RN  - 0 (Cytokines)
RN  - 0 (Fatty Acids, Unsaturated)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Antigen, T-Cell, alpha-beta)
RN  - 0 (Receptors, Retinoic Acid)
RN  - 0 (Retinoid X Receptors)
RN  - 0 (Tetrahydronaphthalenes)
RN  - 0 (Transcription Factors)
RN  - 11103-57-4 (Vitamin A)
RN  - 187348-17-0 (Interleukin-12)
RN  - 1UA8E65KDZ (Alitretinoin)
RN  - 207137-56-2 (Interleukin-4)
RN  - 5688UTC01R (Tretinoin)
SB  - IM
MH  - Alitretinoin
MH  - Animals
MH  - Cells, Cultured
MH  - Cytokines/genetics/physiology
MH  - Dose-Response Relationship, Drug
MH  - Drug Synergism
MH  - Fatty Acids, Unsaturated/pharmacology
MH  - Interleukin-12/antagonists & inhibitors/physiology
MH  - Interleukin-4/pharmacology
MH  - Kinetics
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Transgenic
MH  - RNA, Messenger/biosynthesis
MH  - Receptors, Antigen, T-Cell, alpha-beta/genetics
MH  - Receptors, Retinoic Acid/agonists/*metabolism
MH  - Retinoid X Receptors
MH  - Signal Transduction
MH  - Tetrahydronaphthalenes/pharmacology
MH  - Th1 Cells/drug effects/immunology
MH  - Th2 Cells/drug effects/*immunology
MH  - Transcription Factors/agonists/*metabolism
MH  - Tretinoin/pharmacology
MH  - Vitamin A/*pharmacology
EDAT- 2002/04/24 10:00
MHDA- 2002/05/23 10:01
CRDT- 2002/04/24 10:00
PHST- 2002/04/24 10:00 [pubmed]
PHST- 2002/05/23 10:01 [medline]
PHST- 2002/04/24 10:00 [entrez]
AID - 10.4049/jimmunol.168.9.4495 [doi]
PST - ppublish
SO  - J Immunol. 2002 May 1;168(9):4495-503. doi: 10.4049/jimmunol.168.9.4495.