title: IL-8 and MCP-1 secretion is enhanced by the peptide-nucleic acid immunomodulator, Product R, in U937 cells and primary human monocytes.
abstract: 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.
authors.affiliation: Laboratory of Immunology, Advanced Viral Research Institute, Advanced Viral Research Corp., 200 Corporate Boulevard South, Yonkers, New York 10701, USA.
authors.forename: D A
authors.initials: DA
authors.lastname: Lazzarino
authors.forename: M
authors.initials: M
authors.lastname: de Diego
authors.forename: S Z
authors.initials: SZ
authors.lastname: Hirschman
authors.forename: K Y
authors.initials: KY
authors.lastname: Zhang
authors.forename: S
authors.initials: S
authors.lastname: Shaikh
authors.forename: E
authors.initials: E
authors.lastname: Musi
authors.forename: L
authors.initials: L
authors.lastname: Liaw
authors.forename: R J
authors.initials: RJ
authors.lastname: Alexander
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D018932:Chemokine CCL2 / Q000096:biosynthesis / Q000378:metabolism*; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis / Q000378:metabolism*; D009000:Monocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D020135:Peptide Nucleic Acids / Q000494:pharmacology*; D054390:Receptors, CCR2; D019707:Receptors, Chemokine / Q000096:biosynthesis; D023062:Receptors, Interleukin-8A / Q000096:biosynthesis; D020298:U937 Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*
chemical_list: D000276:Adjuvants, Immunologic; C515334:CCR2 protein, human; D018932:Chemokine CCL2; D016209:Interleukin-8; D020135:Peptide Nucleic Acids; D054390:Receptors, CCR2; D019707:Receptors, Chemokine; D023062:Receptors, Interleukin-8A