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Human Trophoblast‐Derived Exosomal Fibronectin Induces Pro‐Inflammatory Il‐1β Production by Macrophages
Author(s) -
Atay Safinur,
GercelTaylor Cicek,
Taylor Douglas D.
Publication year - 2011
Publication title -
american journal of reproductive immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.071
H-Index - 97
eISSN - 1600-0897
pISSN - 1046-7408
DOI - 10.1111/j.1600-0897.2011.00995.x
Subject(s) - exosome , fibronectin , microvesicles , cytochalasin d , microbiology and biotechnology , trophoblast , cytochalasin b , biology , macrophage , chemistry , immunology , biochemistry , cell , microrna , cytoskeleton , in vitro , extracellular matrix , pregnancy , fetus , genetics , gene , placenta
Citation Atay S, Gercel‐Taylor C, Taylor DD. Human trophoblast‐derived exosomal fibronectin induces pro‐inflammatory Il‐1β production by macrophages. Am J Reprod Immunol 2011; 66: 259–269 Problem Our previous studies demonstrated that trophoblast‐derived exosomes induced synthesis and release of pro‐inflammatory cytokines, including interleukin‐1β (IL‐1β) by macrophages. The objective of this study was to characterize the mechanism and receptors associated with this induction. Method of study Exosomes were isolated from Sw71 trophoblast‐conditioned media by ultrafiltration and ultracentrifugation. Using macrophages isolated from normal donors, cytochalasin D was used to block exosome uptake. Induction of IL‐1β mRNA was investigated by qRT‐PCR, pro‐IL‐1β protein by western immunoblotting, and mature IL‐1β release by ELISA. RGD peptides were used to block fibronectin binding by macrophage α5β1 integrin. Results Uptake of exosomes by macrophages was completely blocked by pre‐treatment with cytochalasin D. Although induction of some cytokines (such as C4A and CCL11) requires uptake, induction of IL‐1β occurred without exosome internalization. Cytochalasin D treatment did not inhibit exosome‐mediated induction of IL‐1β mRNA, production of the pro‐protein, or release of mature IL‐1β. Blocking of fibronectin binding using RGD peptides demonstrated the abrogation of exosome‐mediated IL‐1β production. Conclusion Although trophoblast‐derived exosomes have been demonstrated to induce IL‐1β, this is the first demonstration of IL‐1β induction by exosome‐associated fibronectin. Based on this pro‐inflammatory role of exosome‐associated fibronectin, it may represent an important general immunoregulatory mechanism.