Interleukin 4 production by human amnion epithelial cells and regulation of its activity by glycosaminoglycan binding.
The pro-inflammatory molecules, tumor necrosis factor alpha (TNF alpha), interleukin 1 (IL-1), interleukin 6 (IL-6), and prostaglandin E2 (PGE2), are postulated to have a role in human pregnancy and parturition. The ability of interleukin 4 (IL-4) to suppress the production of TNF alpha, IL-1, IL-6, and PGE2 by activated monocytes prompted us to investigate a possible regulatory role for IL-4 in human gestation. Immunohistochemical techniques were used to show that human amnion epithelium stained positively for IL-4. Tissue from both the first (n = 5) and third (n = 46) trimester expressed immunoreactive IL-4, which was detected by the use of four antihuman IL-4 monoclonal antibodies. Analysis of mRNA by reverse transcriptase-polymerase chain reaction (RT-PCR) on RNA extracts of amnion epithelial cells indicated that they were the source of IL-4. One of the anti-IL-4 antibodies used stained IL-4 protein associated with the basement membrane of the amnion epithelium. The mechanism of this association was investigated. IL-4 was shown to be a heparin-binding cytokine, which would enable it to bind to components of the extracellular matrix. Thus, this study identified a previously undescribed cellular source of IL-4, implicating a role for IL-4 in human gestation. Additionally, glycosaminoglycan binding may regulate IL-4 activity in vivo.
Jones
C A
CA
Department of Microbiology and Infectious Diseases, School of Medicine, Flinders University of South Australia.
Williams
K A
KA
Finlay-Jones
J J
JJ
Hart
P H
PH
D000650:Amnion / Q000378:metabolism*; D001483:Base Sequence; D001485:Basement Membrane / Q000737:chemistry / Q000378:metabolism; D002478:Cells, Cultured; D004848:Epithelium / Q000378:metabolism; D005260:Female; D006025:Glycosaminoglycans / Q000378:metabolism* / Q000494:pharmacology; D006493:Heparin / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D015847:Interleukin-4 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D012333:RNA, Messenger / Q000032:analysis
D006025:Glycosaminoglycans; D012333:RNA, Messenger; D015847:Interleukin-4; D006493:Heparin