Granulocyte-Colony Stimulating Factor and Lipopolysaccharide Regulate the Expression of Interleukin 8 Receptors on Polymorphonuclear Leukocytes

• Published in: The Journal of biological chemistry 1995-11, Vol.270 (47), p.28188-28192
• Main Authors: Lloyd, A R, Biragyn, A, Johnston, J A, Taub, D D, Xu, L, Michiel, D, Sprenger, H, Oppenheim, J J, Kelvin, D J
• Format: Article
• Language: English
• Subjects: Antigens, CD - biosynthesis; Antigens, CD - metabolism; Base Sequence; Blotting, Northern; Cell Nucleus - metabolism; Cells, Cultured; DNA Primers; Escherichia coli; Gene Expression - drug effects; Gene Expression Regulation - drug effects; Granulocyte Colony-Stimulating Factor - pharmacology; Humans; Interleukin-8 - metabolism; Iodine Radioisotopes; Kinetics; Lipopolysaccharides - pharmacology; Molecular Sequence Data; Neutrophils - drug effects; Neutrophils - immunology; Polymerase Chain Reaction; Radioligand Assay; Receptors, Interleukin - biosynthesis; Receptors, Interleukin - metabolism; Receptors, Interleukin-8A; Recombinant Proteins - pharmacology; RNA, Messenger - biosynthesis; RNA, Messenger - blood; Transcription, Genetic - drug effects; Uridine Triphosphate - metabolism
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.270.47.28188

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 I-IL-8 binding. Granulocyte-colony stimulating factor (G-CSF) treatment of PMN enhances, and LPS inhibits, IL-8R mRNA expression. Similarly, I-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.