PMID- 10341317
OWN - NLM
STAT- MEDLINE
DCOM- 19990610
LR  - 20171116
IS  - 1018-2438 (Print)
IS  - 1018-2438 (Linking)
VI  - 119
IP  - 1
DP  - 1999 May
TI  - Soluble human interleukin-4 receptor is produced by activated T cells under the
      control of metalloproteinases.
PG  - 23-30
AB  - BACKGROUND: Soluble interleukin 4 receptors (sIL-4R) are present in biological
      fluids. In contrast to mice, in man no distinct mRNA coding for sIL-4R has been
      described, suggesting that human sIL-4R is exclusively produced by proteolytic
      cleavage of the cell surface receptor. It is not known whether human sIL-4R is
      actively produced during an immune response. METHODS: Human purified T cells,
      CD4+, CD8+, CD45RA+ and CD45R0+ T cell subpopulations were activated in vitro.
      sIL-4R was determined in the supernatants, cell surface IL-4R was measured by
      flow cytometry and RT-PCR. RESULTS: Recombinant sIL-4R inhibited IL-4-mediated
      proliferation and IL-5 upregulation by T cells. sIL-4R could be detected at low
      levels in supernatants of nonactivated T cells, but at high levels following TCR 
      engagement. This response was paralleled by enhanced transcription and de novo
      synthesis of the human cell surface IL-4R. Both, activated naive CD45RA+ and
      memory CD45R0+ T cells, produced sIL-4R with long-lasting kinetics. IL-4
      increased sIL-4R production by activated CD45RA+, but there was less of an
      increase by CD45R0+ T cells. In addition, interferon-gamma enhanced sIL-4R
      production. Cycloheximide and dexamethasone inhibited sIL-4R production by
      activated T cells, but did not abolish constitutive release of sIL-4R.
      Phosphoramidon and 1,10-phenanthroline dose-dependently inhibited shedding of the
      IL-4R, even in nonactivated T cells. CONCLUSION: The production of human sIL-4R
      by T cells is regulated by TCR stimuli, IL-4 and IFN-gamma and needs the activity
      of metalloproteinases. Thus, sIL-4R should be regarded as inducible and due to
      its IL-4-antagonizing activity an immunoregulatory molecule.
FAU - Jung, T
AU  - Jung T
AD  - Department of Dermatology, University of Gottingen, Germany.
      Thomas.Jung@Pharma.Novartis.Com
FAU - Schrader, N
AU  - Schrader N
FAU - Hellwig, M
AU  - Hellwig M
FAU - Enssle, K H
AU  - Enssle KH
FAU - Neumann, C
AU  - Neumann C
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Switzerland
TA  - Int Arch Allergy Immunol
JT  - International archives of allergy and immunology
JID - 9211652
RN  - 0 (Interleukin-5)
RN  - 0 (Receptors, Antigen, T-Cell)
RN  - 0 (Receptors, Interleukin-4)
RN  - 0 (Recombinant Proteins)
RN  - 207137-56-2 (Interleukin-4)
RN  - 82115-62-6 (Interferon-gamma)
RN  - EC 3.1.3.48 (Leukocyte Common Antigens)
RN  - EC 3.4.24.- (Metalloendopeptidases)
SB  - IM
MH  - Animals
MH  - Flow Cytometry
MH  - Humans
MH  - Immunologic Memory
MH  - Interferon-gamma/immunology
MH  - Interleukin-4/immunology
MH  - Interleukin-5/biosynthesis
MH  - Leukocyte Common Antigens/analysis
MH  - *Lymphocyte Activation
MH  - Metalloendopeptidases/*metabolism
MH  - Mice
MH  - Receptors, Antigen, T-Cell/metabolism
MH  - Receptors, Interleukin-4/*biosynthesis/metabolism
MH  - Recombinant Proteins/pharmacology
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Solubility
MH  - T-Lymphocytes/*immunology
MH  - Up-Regulation
EDAT- 1999/05/26 06:00
MHDA- 2000/08/16 11:00
CRDT- 1999/05/26 06:00
PHST- 1999/05/26 06:00 [pubmed]
PHST- 2000/08/16 11:00 [medline]
PHST- 1999/05/26 06:00 [entrez]
AID - 24171 [pii]
AID - 10.1159/000024171 [doi]
PST - ppublish
SO  - Int Arch Allergy Immunol. 1999 May;119(1):23-30. doi: 10.1159/000024171.