Human fetal membrane expression of IL-19 and IL-20 and its differential effect on inflammatory cytokine production.
Objective. The objectives of this study were to document the expression of IL-19 and IL-20, localize their expression in human fetal membranes and to examine their influence on the production of other inflammatory cytokines (IL-1, IL-6, IL-8, and TNF-alpha) from placental membranes.Methods. Human fetal membranes collected at term from normal pregnancies were stimulated with either recombinant human IL-19, IL-20, bacterial endotoxin (LPS) alone or the cytokine + LPS. The expression of IL-19 and IL-20 was studied by reverse transcriptase polymerase chain reaction (RT-PCR) and localized using immunohistochemistry. Concentrations of IL-1, IL-6, IL-8, and TNF-alpha were measured with multiplex sandwich immunoassay using microsphere technology.Results. RT-PCR documented IL-19 and IL-20 gene expression in fetal membranes. Immunohistochemistry localized both peptides to amnion and chorion layers. LPS stimulated the production of all four cytokines (IL-1, IL-6, IL-8, and TNF-alpha) from fetal membranes compared to unstimulated controls. No change in IL-1 and IL-8 concentration was seen after IL-19 or IL-20 stimulation, whereas IL-6 concentration was three- and two-fold higher after IL-19 and IL-20 treatment, respectively. TNF levels were unchanged after IL-19 and IL-20 treatment; however, TNF levels were significantly decreased in membranes treated with IL-19 or IL-20 + LPS compared to LPS alone.Conclusion. Fetal membranes are a source of IL-19 and IL-20. These cytokines act as an inhibitory agent to LPS-induced TNF production whereas they stimulate IL-6 production and have no effect on IL-1 and IL-8 production from human fetal membranes. The effect of IL-19 and IL-20 in pregnancy will be dependent on their concentrations and other environmental factors such as infection.
Menon
Ramkumar
R
Perinatal Research Center of the Women's Health Research and Education Foundation, 2300 Patterson Street, Nashville, TN 37203, USA.
Ismail
Lana
L
Ismail
Deema
D
Merialdi
Mario
M
Lombardi
Salvatore J
SJ
Fortunato
Stephen J
SJ
D016207:Cytokines / Q000378:metabolism*; D005321:Extraembryonic Membranes / Q000378:metabolism*; D005260:Female; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D007378:Interleukins / Q000378:metabolism* / Q000502:physiology; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D047929:Term Birth / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016207:Cytokines; C421250:IL19 protein, human; D007375:Interleukin-1; D015850:Interleukin-6; D016209:Interleukin-8; D007378:Interleukins; D014409:Tumor Necrosis Factor-alpha; C422042:interleukin 20