IL-8 and MCP-1 secretion is enhanced by the peptide-nucleic acid immunomodulator, Product R, in U937 cells and primary human monocytes.
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.
Lazzarino
D A
DA
Laboratory of Immunology, Advanced Viral Research Institute, Advanced Viral Research Corp., 200 Corporate Boulevard South, Yonkers, New York 10701, USA.
de Diego
M
M
Hirschman
S Z
SZ
Zhang
K Y
KY
Shaikh
S
S
Musi
E
E
Liaw
L
L
Alexander
R J
RJ
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*
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