Trophoblast-derived exosomes mediate monocyte recruitment and differentiation.
BACKGROUND
trophoblast cells have been demonstrated to regulate monocyte migration and differentiation, leading to pro-inflammatory profiles. Because trophoblast cells release exosomes with immunoregulatory properties, trophoblast-derived exosomes are proposed to 'educate' monocytes, creating a pro-inflammatory environment.


METHODS
exosomes were isolated from conditioned media of Swan71 cells by ultrafiltration and ultracentrifugation. Exosome-induced migration was assessed using a two-chamber system. Cytokine profiles were defined using cytokine arrays, and mRNA levels of affected cytokines were examined by qRT-PCR and ELISA.


RESULTS
within 20 min, 8-10% of monocytes took up labeled exosomes isolated from Swan71 cells. Trophoblast-derived exosomes increased monocyte migration in a dose-dependent manner and produced significant increases in production of interleukin (IL)-1β, IL-6, Serpin-E1, granulocyte colony-stimulating factor, granulocyte/monocyte colony-stimulating factor, and tumor necrosis factor-α.


CONCLUSIONS
this study presents the initial demonstration that trophoblast-derived exosomes are capable of recruiting and 'educating' monocytes to produce pro-inflammatory cytokine/chemokine profiles in a cell-contact-independent manner.
Atay
Safinur
S
Departments of Microbiology & Immunology, University of Louisville, Louisville, KY 40202, USA.
Gercel-Taylor
Cicek
C
Suttles
Jill
J
Mor
Gil
G
Taylor
Douglas D
DD
D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology; D018925:Chemokines / Q000096:biosynthesis; D055354:Exosomes / Q000502:physiology*; D005260:Female; D005786:Gene Expression Regulation; D016179:Granulocyte Colony-Stimulating Factor / Q000096:biosynthesis; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D008264:Macrophages / Q000166:cytology; D009000:Monocytes / Q000166:cytology / Q000502:physiology*; D017395:Plasminogen Activator Inhibitor 1 / Q000096:biosynthesis; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics; D014327:Trophoblasts / Q000166:cytology / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D018925:Chemokines; D007375:Interleukin-1; D015850:Interleukin-6; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor