Activated peripheral blood mononuclear cells induce p44/42 mitogen-activated protein kinase phosphorylation in trophoblast-like JAR cells.
Mammalian pregnancy bears many similarities to transplantation, since the fetus is semi-allogenic to mother. Thus, mammals have developed numerous mechanisms to protect the developing fetus from maternal immunologic recognition and attack. We have previously shown that human choriocarcinoma JAR cells, which resemble first trimester trophoblasts, regulate several important mRNAs in activated peripheral blood mononuclear cells (PBMC). We now provide further evidence that communication between maternal and fetal tissues is bi-directional, and that activation of PBMC leads to activation of specific signaling pathways in JAR cells. Activated PBMC were co-cultured with JAR cells for specific time intervals, after which JAR cells were lysed and subjected to western blotting for activated forms of the JNK, Erk 1-2, and p38 mitogen-activated protein kinases (MAPK). Phosphorylation of Erk 1-2, but not JNK or p38, was induced in co-cultures of PBMC and JAR cells. These results were also obtained when JAR cells were incubated with conditioned medium from activated, but not resting, PBMC. Results were confirmed using specific MAPK reporter constructs, using luciferase activity as a measure of Elk-1 phosphorylation. Erk 1-2 phosphorylation was not required for JAR cells to inhibit IL-2 production in activated PBMC. Addition of the specific MAPK inhibitor UO126 to JAR cells prior to the addition of activated PBMC to the cultures did not abolish the capacity of JAR cells to inhibit IL-2 mRNA expression in PBMC. We conclude that there is likely to be significant bi-directional signaling between leukocytes and trophoblasts at the maternal-fetal interface. We propose the existence of a delicate maternal-fetal immunologic homeostasis based on these experimental results.
Jiang
Kaiyu
K
Department of Pediatrics, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
Chen
Yanmin
Y
Jarvis
James N
JN
D001483:Base Sequence; D002460:Cell Line; D018920:Coculture Techniques; D017077:Culture Media, Conditioned; D053222:Fas Ligand Protein; D005260:Female; D017930:Genes, Reporter; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D007376:Interleukin-2 / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008156:Luciferases / Q000235:genetics; D008562:Membrane Glycoproteins / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D010766:Phosphorylation; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics; D011994:Recombinant Proteins / Q000494:pharmacology; D014327:Trophoblasts / Q000166:cytology / Q000201:enzymology* / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D017077:Culture Media, Conditioned; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D007376:Interleukin-2; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D008156:Luciferases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases