Hyaluronan carried by tumor-derived microvesicles induces IL-10 production in classical (CD14++CD16-) monocytes via PI3K/Akt/mTOR-dependent signalling pathway.
Immunobiology
; 222(1): 1-10, 2017 01.
Article
in En
| MEDLINE
| ID: mdl-26210045
ABSTRACT
Tumor-derived microvesicles (TMV) can mimic effects of tumor cells leading to an increased anti-inflammatory cytokine production, such as interleukin 10 (IL-10), by tumor-infiltrating monocytes and macrophages. Yet, the mechanism of IL-10 induction by TMV in monocytes remains unclear. The co-incubation of TMV derived from the human pancreas carcinoma cell line (HPC-4) with human monocytes resulted in a nearly 30-fold increase in IL-10 protein production. This effect operates at the level of transcription since monocytes transduced with an adenovirus containing IL-10-promoter luciferase reporter gene showed a 5-fold induction of luciferase activity after treatment with TMV. Since tumor cells can express hyaluronan (HA), which participates in tumor invasion and metastases, we have tested its effect on IL-10 expression. We showed that HA at the concentration of 100µg/ml induces IL-10 protein expression and the IL-10 promoter activation in monocytes. Moreover, hyaluronidase treatment of TMV reduced IL-10 protein production by 50% and promoter activity by 40%. Inhibitors of the PI3K/Akt/mTOR pathway reduced both, TMV-induced IL-10 promoter activity and protein production, and the same was observed in monocytes when stimulated by HPC-4 cells or HA. Inhibition of PI3K activity down-regulated phosphorylation of the Akt and (to a lesser extent) mTOR proteins in monocytes following TMV or HA stimulation. When comparing monocyte subsets, TMV induced IL-10 protein and mRNA synthesis only in classical CD14++CD16- but not in CD16-positive monocytes. Our data show that TMV induce IL-10 synthesis in human classical monocytes via HA, which, in turn, activates the PI3K/Akt/mTOR pathway.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Monocytes
/
Signal Transduction
/
Interleukin-10
/
Phosphatidylinositol 3-Kinases
/
Proto-Oncogene Proteins c-akt
/
Cell-Derived Microparticles
/
TOR Serine-Threonine Kinases
/
Hyaluronic Acid
Type of study:
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
Immunobiology
Year:
2017
Document type:
Article
Affiliation country:
Polonia