Comparative proteomic study reveals the enhanced immune response with the blockade of interleukin 10 with anti-IL-10 and anti-IL-10 receptor antibodies in human U937 cells

Guoying Ni; Shu Chen; Jianwei Yuan; Shelley F Cavezza; Ming Q Wei; Hejie Li; Xuan Pan; Xiaosong Liu; Tianfang Wang

doi:10.1371/journal.pone.0213813

Comparative proteomic study reveals the enhanced immune response with the blockade of interleukin 10 with anti-IL-10 and anti-IL-10 receptor antibodies in human U937 cells

PLoS One. 2019 Mar 21;14(3):e0213813. doi: 10.1371/journal.pone.0213813. eCollection 2019.

Authors

Guoying Ni^{1

2

3}, Shu Chen⁴, Jianwei Yuan¹, Shelley F Cavezza⁵, Ming Q Wei³, Hejie Li⁶, Xuan Pan¹, Xiaosong Liu^{1

4

5}, Tianfang Wang²

Affiliations

¹ The First Affiliated Hospital/School of Clinical Medicine of Guangdong Pharmaceutical University, Guangzhou, China.
² Genecology Research Centre, University of the Sunshine Coast, Maroochydore DC, Australia.
³ School of Medical Science, Griffith Health Institute, Griffith University, Gold Coast, Australia.
⁴ Cancer Research Institute, First People's Hospital of Foshan, Foshan, Guangdong, China.
⁵ School of Health and Sport Sciences, University of the Sunshine Coast, Maroochydore DC, Australia.
⁶ Institute of Industrial Science, Department of Mechanical and Bio-functional System, the University of Tokyo, Tokyo, Japan.

Abstract

Blocking cytokine interleukin 10 (IL-10) at the time of immunisation enhances vaccine induced T cell responses and improves control of tumour cell growth in vivo. However, the effect of an IL-10 blockade on the biological function of macrophages has not been explored. In the current paper, a macrophage precursor cell line, U937 cells, was selected to investigate the differential expression of proteins and relevant cell signalling pathway changes, when stimulated with lipopolysaccharide (LPS) in the presence of antibodies to IL-10 or IL-10 receptor. We used a quantitative proteomic strategy to investigate variations in protein profiles of U937 cells following the treatments with LPS, LPS plus human anti-IL10 antibody and anti-IL10R antibody in 24hrs, respectively. The LPS treatment significantly activated actin-related cell matrix formation and immune response pathways. The addition of anti-IL10 and anti-IL10R antibody further promoted the immune response and potentially effect macrophage survival through PI3K/AKT signalling; however, the latter appeared to also upregulated oncogene XRCC5 and Cajal body associated processes.

Publication types

Comparative Study
Research Support, Non-U.S. Gov't

MeSH terms

Antibodies, Monoclonal / pharmacology*
Cell Proliferation / drug effects
Gene Expression Regulation / drug effects*
Humans
Interleukin-10 / antagonists & inhibitors*
Interleukin-10 / immunology
Macrophages / drug effects
Macrophages / immunology
Macrophages / metabolism*
Protein Interaction Maps
Proteome / analysis*
Proteomics
Receptors, Interleukin-10 / antagonists & inhibitors*
Receptors, Interleukin-10 / immunology
Signal Transduction / drug effects*
U937 Cells

Substances

Antibodies, Monoclonal
IL10 protein, human
Proteome
Receptors, Interleukin-10
Interleukin-10

Grants and funding

This study was supported by: National Natural Science Foundation of China, award number: 81472451, recipient: Xiaosong Liu; Guangdong Provincial Government, award number: 2016A020213001, recipient: Xiaosong Liu; Foshan Municipal Government, award number: 2012AA100461, recipient: Xiaosong Liu; Foshan Municipal Government, award number: 2015AG1003, recipient: Xiaosong Liu. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.