Inhibition of U937 Cytokine Secretion by HIV-1 gp120 C4-Derived Peptide Constructs

Abstract

Lipopolysaccharide (LPS) stimulation of the human promyelomonocytic cell line U937 results in interleukin 6 and interleukin 10 secretion. Modulation of cytokine secretion in response to LPS may be possible through binding of ligands to surface receptors. A peptomer, containing multiple repeat units of the CD4-binding C4 region of HIV-1 gp120, and the monomeric C4 peptide each were investigated for their ability to affect LPSinduced IL-6 and IL-10 secretion. The peptomer inhibited IL-6 and IL-10 secretion, while the monomer inhibited only IL-6 secretion. Larger CD4-binding proteins, specifically gp120 and Leu3A, a CD4-directed monoclonal antibody, had no effect on the LPS response. PMA differentiation to downregulate CD4 expression did not reverse the inhibitory effect of the peptomer or peptide, suggesting a CD4-independent effect. Bioactivity changed markedly with different constructs in the presence of IFN. with reversal or enhancement of the IL-10 response but not IL-6 production. These results suggest that truncation of a larger polypeptide may result in constructs with novel binding capabilities and bioactivities not seen in parent proteins.