Granulocyte-colony stimulating factor and lipopolysaccharide regulate the expression of interleukin 8 receptors on polymorphonuclear leukocytes.
Interleukin 8 (IL-8) is a potent chemoattractant and activating factor for human polymorphonuclear leukocytes (PMN) and hence plays a critical role in the pathogenesis of acute inflammation. Two unique but homologous receptors for IL-8 have been cloned (IL-8RA and -B), each of which binds the IL-8 ligand with high affinity. PMN stimulated by cytokines or lipopolysaccharide (LPS) exhibit changes in IL-8R mRNA and 125I-IL-8 binding. Granulocyte-colony stimulating factor (G-CSF) treatment of PMN enhances, and LPS inhibits, IL-8R mRNA expression. Similarly, 125I-IL-8 ligand binding to PMN is increased by G-CSF and decreased by LPS treatment. The stimulatory effect of G-CSF on IL-8R expression is transcriptional as it is inhibited by actinomycin D and is evident in nuclear run-on analyses. In contrast, LPS down-regulates IL-8R by both transcriptional and post-transcriptional mechanisms. The alterations in IL-8R expression are associated with similar changes in the IL-8-induced chemotactic responses of PMN. In conclusion, the two types of IL-8 receptor differ in their cellular distribution and are regulated in response to cytokines and LPS. Regulation of IL-8R expression by endogenous and exogenous immunomodulators may be important in the in vivo control of PMN effector functions in inflammation.
D015703:Antigens, CD / Q000096:biosynthesis* / Q000378:metabolism; D001483:Base Sequence; D015152:Blotting, Northern; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D017931:DNA Primers; D004926:Escherichia coli; D015870:Gene Expression / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D007457:Iodine Radioisotopes; D007700:Kinetics; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008969:Molecular Sequence Data; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis / Q000097:blood; D011869:Radioligand Assay; D018123:Receptors, Interleukin / Q000096:biosynthesis* / Q000378:metabolism; D023062:Receptors, Interleukin-8A; D011994:Recombinant Proteins / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects; D014544:Uridine Triphosphate / Q000378:metabolism
D015703:Antigens, CD; D017931:DNA Primers; D016209:Interleukin-8; D007457:Iodine Radioisotopes; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D023062:Receptors, Interleukin-8A; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D014544:Uridine Triphosphate