Tumour necrosis factor alpha stimulates the production of monocyte chemoattractants by extravillous trophoblast cells via differential activation of MAPK pathways.
The decidual microenvironment is characterized by a unique population of leukocytes composed primarily of CD56(bright) NK cells and macrophages. The latter are situated near trophoblast cells at the fetal-maternal interface and there is evidence that trophoblast cells are capable of recruiting macrophages to this site. This study sought to determine the role of tumour necrosis factor alpha (TNF) in the trophoblast-mediated recruitment of monocyte-derived macrophages to the fetal-maternal interface. The human first trimester extravillous trophoblast cell line HTR-8/SVneo was shown to express TNFR1 and to secrete the monocyte-attracting chemokines CCL2 and CCL5 after exposure to TNF in a dose-dependent manner. TNF-mediated stimulation of CCL2 secretion was completely inhibited by incubating the trophoblast cells with the p38-MAPK inhibitor SB203580, whereas CCL5 secretion was inhibited by treating the trophoblast cells with inhibitors specific for JNK (SP600125) and ERK kinase (U0126). Media conditioned by TNF-treated trophoblast cells significantly enhanced the ability of the monocyte cell line THP-1 to invade through Matrigel, and this effect was inhibited using antibodies specific for CCL2 and CCL5. These results support a role for TNF at the fetal-maternal interface as a regulator of macrophage recruitment by trophoblast cells.
Renaud
S J
SJ
Department of Anatomy and Cell Biology, Queen's University, Kingston, ON, Canada K7L 3N6.
Sullivan
R
R
Graham
C H
CH
D000873:Anthracenes / Q000494:pharmacology; D002070:Butadienes / Q000494:pharmacology; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D018932:Chemokine CCL2 / Q000096:biosynthesis*; D018946:Chemokine CCL5 / Q000096:biosynthesis*; D003094:Collagen; D017077:Culture Media, Conditioned; D004338:Drug Combinations; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D007797:Laminin; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D009570:Nitriles / Q000494:pharmacology; D011247:Pregnancy; D011509:Proteoglycans; D011725:Pyridines / Q000494:pharmacology; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000378:metabolism; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000378:metabolism; D014327:Trophoblasts / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D000873:Anthracenes; D002070:Butadienes; C111835:CCL2 protein, human; C483024:CCL5 protein, human; D018932:Chemokine CCL2; D018946:Chemokine CCL5; D017077:Culture Media, Conditioned; D004338:Drug Combinations; D004791:Enzyme Inhibitors; D007093:Imidazoles; D007797:Laminin; D009570:Nitriles; D011509:Proteoglycans; D011725:Pyridines; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha; C113580:U 0126; C059485:matrigel; C432165:pyrazolanthrone; D003094:Collagen; C093642:SB 203580