Regulation of I‐309 gene expression in human monocytes by endogenous interleukin‐1

摘要

AbstractActivated human monocytes are a source of numerous γ‐chemokines. The present study was conducted to determine whether these cells produce the human γ‐chemokine I‐309 and to compare the induction requirements of I‐309 to those of other γ‐chemokines. We demonstrate that appropriately stimulated adherence‐purified human peripheral blood monocytes express I‐309 transcripts and secreted I‐309 protein. Two stimuli, immobilized IgG and lipopolysaccharide (LPS), synergize strongly to induce I‐309 gene expression. We further demonstrate that the production of endogenous interleukin (IL)‐1α plays a crucial role in I‐309 induction. Thus, neutralization of endogenous IL‐1α using an anti‐IL‐1α antiserum inhibits the induction of I‐309 transcripts in response to stimulation with immobilized IgG and LPS, and exogenous IL‐1α or IL‐1β induces I‐309 transcripts in monocytes stimulated with immobilized IgG. Immobilized IgG and LPS have the opposite effect on monocyte chemoattractant protein‐1 (MCP‐1) gene expression, in that the induction observed with either stimulus alone is diminished using the two stimuli in combination. Furthermore, endogenous and exogenous IL‐1 can be either stimulatory or inhibitory for MCP‐1 gene expression depending on other signals delivered to the monocytes. Immobilized IgG and LPS synergize to induce macrophage inflammatory protein‐1α transcripts, but endogenous IL‐1 does not play a significant role. Thus, each of these γ‐chemokine ge