Modulation of interleukin-8 receptor expression by lipopolysaccharide (LPS) and phorbol myristate acetate (PMA) in...

Interleukin-8, a monocyte derived neutrophil chemotactic agent is known to play as a key mediator in the pathogenesis of a large number of neutrophil driven inflammatory diseases. Since the cytokine activates the target cells through a cell surface receptor, study of the regulation of IL-8 receptor expression in monocytes is very important. We found that two very known modulators, lipopolysaccharide (LPS) in presence of homologous serum and Phorbol myristate acetate (PMA) resulted in induction of IL-8 receptor by 100-120% and 75-125% respectively within 1 h in monocytes. Based on the inhibitory effect of cycloheximide, actinomycin-D we may suggest that PMA and LPS could upregulate IL-8 receptor in monocytes through denovo protein synthesis. Prior incubation of polymixin B and anti-CD-14 antibody to the monocytes and subsequent stimulation of the cells with ser.act.LPS resulted in > 90% inhibition of IL-8 binding. Scatchard analysis showed that estimated receptor number in control cell was 7,500 per cell and it increased to 15,500 per cell in ser.act.LPS stimulated cell. The receptor number in PMA stimulated cells was 13,000 per cell. Chemical cross-linking of the IL-8 receptor with 125I labelled IL-8 in the ser.act.LPS and PMA stimulated cells-indicated that the signals at 59 kD were considerably increased with respect to control. A correlation between LPS and ser.act.LPS induced upregulation of IL-8 receptor expression has been shown. The study with bacterial product and co-carcinogenic agent thus provides information about the differential expression of IL-8 receptor for sustained IL-8 mediated biological response.