Regulation of I-309 gene expression in human monocytes by endogenous interleukin-1.
Activated human monocytes are a source of numerous beta-chemokines. The present study was conducted to determine whether these cells produce the human beta-chemokine I-309 and to compare the induction requirements of I-309 to those of other beta-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)-1alpha plays a crucial role in I-309 induction. Thus, neutralization of endogenous IL-1alpha using an anti-IL-1alpha antiserum inhibits the induction of I-309 transcripts in response to stimulation with immobilized IgG and LPS, and exogenous IL-1alpha or IL-1beta 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-1alpha transcripts, but endogenous IL-1 does not play a significant role. Thus, each of these beta-chemokine genes is under distinct regulatory control in human monocytes.
Selvan
R S
RS
Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA. selva001@mc.duke.edu
Zhou
L J
LJ
Krangel
M S
MS
D002448:Cell Adhesion; D002478:Cells, Cultured; D054402:Chemokine CCL1; D018932:Chemokine CCL2 / Q000235:genetics; D054407:Chemokine CCL4; D018925:Chemokines / Q000235:genetics*; D019742:Chemokines, CC; D015870:Gene Expression; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology; D007375:Interleukin-1 / Q000502:physiology; D008070:Lipopolysaccharides / Q000494:pharmacology; D019402:Macrophage Inflammatory Proteins / Q000235:genetics; D009000:Monocytes / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D014158:Transcription, Genetic
C065971:CCL1 protein, human; D054402:Chemokine CCL1; D018932:Chemokine CCL2; D054407:Chemokine CCL4; D018925:Chemokines; D019742:Chemokines, CC; D007074:Immunoglobulin G; D007375:Interleukin-1; D008070:Lipopolysaccharides; D019402:Macrophage Inflammatory Proteins; D012333:RNA, Messenger