PuSH - Publication Server of Helmholtz Zentrum München

Lenart, M.* ; Rutkowska-Zapala, M.* ; Baj-Krzyworzeka, M.* ; Szatanek, R.* ; Węglarczyk, K.* ; Smallie, T.* ; Ziegler-Heitbrock, L. ; Zembala, M.* ; Siedlar, M.*

Hyaluronan carried by tumor-derived microvesicles induces IL-10 production in classical CD14++ CD16- monocytes via PI3K/Akt/mTOR-dependent signalling pathway.

Immunobiology 222, 1-10 (2015)
DOI PMC
Open Access Gold as soon as Publ. Version/Full Text is submitted to ZB.
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.
Impact Factor
Scopus SNIP
Web of Science
Times Cited
Scopus
Cited By
Altmetric
3.044
0.866
21
21
Tags
Annotations
Special Publikation
Hide on homepage

Edit extra information
Edit own tags
Private
Edit own annotation
Private
Hide on publication lists
on hompage
Mark as special
publikation
Publication type Article: Journal article
Document type Scientific Article
Keywords Hyaluronan ; Il-10 ; Monocyte Subsets ; Monocytes ; Pi3k/akt/mtor Pathway ; Tumor-derived Microvesicles,; Gene-expression; Dendritic Cells; Phosphatidylinositol-3 Kinase; Inflammatory Response; Transcription Factor; Cancer-cells; Macrophages; Activation; Lipopolysaccharide; Differentiation
Language
Publication Year 2015
HGF-reported in Year 2015
ISSN (print) / ISBN 0171-2985
e-ISSN 1878-3279
Quellenangaben Volume: 222, Issue: 1, Pages: 1-10 Article Number: , Supplement: ,
Publisher Urban & Fischer
Publishing Place Jena
Reviewing status Peer reviewed
POF-Topic(s) 30503 - Chronic Diseases of the Lung and Allergies
Research field(s) Lung Research
PSP Element(s) G-501690-001
PubMed ID 26210045
Scopus ID 84957729518
Scopus ID 84937510083
Erfassungsdatum 2015-07-28