PMID- 16448625
OWN - NLM
STAT- MEDLINE
DCOM- 20060425
LR  - 20061115
IS  - 0006-2952 (Print)
IS  - 0006-2952 (Linking)
VI  - 71
IP  - 8
DP  - 2006 Apr 14
TI  - Inhibition of interleukin-4 production in activated T cells via the 
      downregulation of AP-1/NF-AT activation by N-lauroyl-D-erythro-sphingosine and 
      N-lauroyl-D-erythro-C20-sphingosine.
PG  - 1229-39
AB  - Allergic diseases are hypersensitivity disorders that are associated with the 
      generation of specific immunoglobulin E (IgE) in response to environmental 
      allergens. Interleukin (IL)-4, which is primarily produced by the CD4(+) T cells, 
      is an important stimulus for the switching of the antibody isotype to IgE in both 
      mice and humans. In a previous study, we demonstrated that ceramide derivatives 
      coupled with a lauroyl group exerted strong inhibitory effects on IL-4 production 
      in T cells. In this study, we attempted to characterize the mechanisms underlying 
      the inhibition of IL-4 production in T cells. Two ceramide derivatives, 
      N-lauroyl-D-erythro-sphingosine and N-lauroyl-D-erythro-C(20)-sphingosine 
      (hereafter abbreviated as LES and LECS, respectively), were shown to 
      significantly inhibit the production of IL-4 in both primary CD4(+) T cells and 
      EL4 T thymoma cells in a dose-dependent manner. LES and LECS also inhibited the 
      activity of the IL-4 gene promoter in EL4 cells transiently transfected with IL-4 
      gene promoter constructs, but this effect was impaired in EL4 cells that had been 
      transfected with an IL-4 promoter construct deleted of a P4 site harboring the 
      AP-1 and NF-AT binding sites. Furthermore, LES and LECS inhibited the DNA binding 
      activities of both AP-1 and NF-AT transcription factors. In addition, LES and 
      LECS were demonstrated to suppress PMA-stimulated PKC activity, although they 
      exerted no significant effects on the protein levels of the conventional PKCs. 
      These results indicate that the ceramides, LES and LECS, may inhibit the 
      production of IL-4 in the activated T cells, via the downregulation of AP-1/NF-AT 
      activation and PKC activity.
FAU - Park, Jin
AU  - Park J
AD  - School of Life Sciences and Biotechnology, Korea University, Seoul, Republic of 
      Korea.
FAU - Kim, Seung Hyun
AU  - Kim SH
FAU - Li, Qian
AU  - Li Q
FAU - Chang, Young-Tae
AU  - Chang YT
FAU - Kim, Tae Sung
AU  - Kim TS
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20060131
PL  - England
TA  - Biochem Pharmacol
JT  - Biochemical pharmacology
JID - 0101032
RN  - 0 (Ceramides)
RN  - 0 (NFATC Transcription Factors)
RN  - 0 (Transcription Factor AP-1)
RN  - 207137-56-2 (Interleukin-4)
RN  - 74713-60-3 (N-lauroylsphingosine)
SB  - IM
MH  - Animals
MH  - CD4-Positive T-Lymphocytes/*drug effects/immunology/metabolism
MH  - Cell Line, Tumor
MH  - Ceramides/chemistry/*pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Down-Regulation
MH  - Interleukin-4/*metabolism
MH  - Lymphocyte Activation/*drug effects/immunology
MH  - Mice
MH  - NFATC Transcription Factors/*metabolism
MH  - Stereoisomerism
MH  - Transcription Factor AP-1/*metabolism
EDAT- 2006/02/02 09:00
MHDA- 2006/04/28 09:00
CRDT- 2006/02/02 09:00
PHST- 2005/11/21 00:00 [received]
PHST- 2005/12/27 00:00 [revised]
PHST- 2005/12/29 00:00 [accepted]
PHST- 2006/02/02 09:00 [pubmed]
PHST- 2006/04/28 09:00 [medline]
PHST- 2006/02/02 09:00 [entrez]
AID - S0006-2952(06)00007-4 [pii]
AID - 10.1016/j.bcp.2005.12.036 [doi]
PST - ppublish
SO  - Biochem Pharmacol. 2006 Apr 14;71(8):1229-39. doi: 10.1016/j.bcp.2005.12.036. 
      Epub 2006 Jan 31.