Journal
CELLULAR AND MOLECULAR LIFE SCIENCES
Volume 71, Issue 20, Pages 4055-4067Publisher
SPRINGER BASEL AG
DOI: 10.1007/s00018-014-1618-z
Keywords
Extracellular vesicle; Inflammation; Interleukin-8; Microarray; TNF
Categories
Funding
- OTKA NK [84043]
- OTKA [PD104369]
- Marie Curie Networks for Initial Training-ITN-FP7-PEOPLE-ITN [PITN-GA-2011-289033]
- TAMOP [4.2.4. A/1-11-1-2012-0001]
- European Union
- European Social Fund
- [REG-KM-09-1-2009-0010]
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Under physiological and pathological conditions, extracellular vesicles (EVs) are present in the extracellular compartment simultaneously with soluble mediators. We hypothesized that cytokine effects may be modulated by EVs, the recently recognized conveyors of intercellular messages. In order to test this hypothesis, human monocyte cells were incubated with CCRF acute lymphoblastic leukemia cell line-derived EVs with or without the addition of recombinant human TNF, and global gene expression changes were analyzed. EVs alone regulated the expression of numerous genes related to inflammation and signaling. In combination, the effects of EVs and TNF were additive, antagonistic, or independent. The differential effects of EVs and TNF or their simultaneous presence were also validated by Taqman assays and ELISA, and by testing different populations of purified EVs. In the case of the paramount chemokine IL-8, we were able to demonstrate a synergistic upregulation by purified EVs and TNF. Our data suggest that neglecting the modulating role of EVs on the effects of soluble mediators may skew experimental results. On the other hand, considering the combined effects of cytokines and EVs may prove therapeutically useful by targeting both compartments at the same time.
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