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

• Published in: PloS one Vol. 14; no. 3; p. e0213813
• Main Authors: Ni, Guoying, Chen, Shu, Yuan, Jianwei, Cavezza, Shelley F, Wei, Ming Q, Li, Hejie, Pan, Xuan, Liu, Xiaosong, Wang, Tianfang
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 21.03.2019; Public Library of Science (PLoS)
• Subjects: 1-Phosphatidylinositol 3-kinase; Actin; AKT protein; Analysis; Antibodies; Antibodies, Monoclonal - pharmacology; Biology; Biology and Life Sciences; Cancer; Cell Proliferation - drug effects; Cell survival; Cellular signal transduction; Clinical medicine; Computer and Information Sciences; Cytokines; Gene Expression Regulation - drug effects; Hospitals; Humans; Immune response; Immune system; Immunization; Immunoglobulins; Interleukin 1; Interleukin 10; Interleukin 10 receptors; Interleukin-10 - antagonists & inhibitors; Interleukin-10 - immunology; Interleukins; Kinases; Lipopolysaccharides; Lymphocytes; Lymphocytes T; Macrophages; Macrophages - drug effects; Macrophages - immunology; Macrophages - metabolism; Medical research; Medicine; Medicine and Health Sciences; Mitogens; Muscle proteins; Peptides; Pharmaceuticals; Protein Interaction Maps; Proteins; Proteome - analysis; Proteomics; Receptors, Interleukin-10 - antagonists & inhibitors; Receptors, Interleukin-10 - immunology; Research and Analysis Methods; Signal transduction; Signal Transduction - drug effects; Signaling; T cells; Tumors; U937 Cells; Vaccines; Australia; China
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0213813

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.