IL-8 and MCP-1 secretion is enhanced by the peptide-nucleic acid immunomodulator, Product R, in U937 cells and primary human monocytes

Cytokine. 2001 May 21;14(4):234-9. doi: 10.1006/cyto.2001.0867.

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.

MeSH terms

  • Adjuvants, Immunologic / pharmacology*
  • Apoptosis / drug effects
  • Apoptosis / immunology
  • Chemokine CCL2 / biosynthesis
  • Chemokine CCL2 / metabolism*
  • Humans
  • 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*

Substances

  • Adjuvants, Immunologic
  • CCR2 protein, human
  • Chemokine CCL2
  • Interleukin-8
  • Peptide Nucleic Acids
  • Receptors, CCR2
  • Receptors, Chemokine
  • Receptors, Interleukin-8A
  • reticulose