IL-8 AND MCP-1 SECRETION IS ENHANCED BY THE PEPTIDE-NUCLEIC ACID IMMUNOMODULATOR, PRODUCT R, IN U937 CELLS AND PRIMARY HUMAN MONOCYTES

• Published in: Cytokine (Philadelphia, Pa.) Pa.), 2001-05, Vol.14 (4), p.234-239
• Main Authors: Lazzarino, Deborah A., de Diego, Maribel, Hirschman, Shalom Z., Zhang, Katie Y., Shaikh, Seema, Musi, Elgilda, Liaw, Lilian, Alexander, Richard J.
• Format: Article
• Language: English
• Subjects: Adjuvants, Immunologic - pharmacology; Apoptosis - drug effects; Apoptosis - immunology; Chemokine CCL2 - biosynthesis; Chemokine CCL2 - metabolism; Humans; IL-8/immunomodulator/MCP-1/monocytes/Product R; Interleukin-8 - biosynthesis; Interleukin-8 - metabolism; Monocytes - drug effects; Monocytes - immunology; Monocytes - metabolism; Peptide Nucleic Acids - pharmacology; Receptors, CCR2; Receptors, Chemokine - biosynthesis; Receptors, Interleukin-8A - biosynthesis; U937 Cells - drug effects; U937 Cells - immunology; U937 Cells - metabolism
• ISSN: 1043-4666; 1096-0023
• DOI: 10.1006/cyto.2001.0867

Product R (Reticulose™) is a peptide–nucleic acid immunomodulator recently shown to enhance the expression of mRNAs encoding pro-inflammatory cytokines. Interleukin 8 (IL-8) and macrophage chemoattractant protein-1 (MCP-1) are pro-inflammatory chemokines involved in immune cell mobilization and stimulation. To determine whether Product R acts by upregulating these chemokines, we assayed its effects on the expression of IL-8 and MCP-1 mRNAs and proteins by human monocytic U937 cells and by adherent peripheral blood mononuclear cells (PBMCs). U937 cells were cultured for 0–21 days in media containing 0–20% Product R or phosphate-buffered saline (PBS). Compared to control cultures, cells cultured in Product R expressed increased amounts of IL-8 and MCP-1 mRNAs, as measured by reverse transcriptase-polymerase chain reaction (RT-PCR). Product R also increased secretion of IL-8 and MCP-1, as measured by enzyme-linked immunosorbent assay (ELISA), and boosted secretion induced by bacterial lipopolysaccharide (LPS), in a time- and dose-dependent manner. In adherent PBMCs, Product R increased IL-8 and MCP-1 secretion, but reduced LPS-induced MCP-1 secretion. While mRNAs encoding the IL-8 receptor, CXCR2, and the MCP-1 receptor, CCR2, were increased in U937 cells cultured in 5–10% Product R, we observed no change in binding of receptor-specific antibodies. These findings suggest that Product R upregulates the expression of IL-8 and MCP-1, which may boost immune system activity in virally-infected patients.