title: Peripheral blood neutrophil production of interleukin-1 receptor antagonist and interleukin-1 beta.
abstract: The objective of this study was to characterize interleukin-1 receptor antagonist (IL-1ra) and interleukin-1 beta (IL-1 beta) production by human peripheral blood neutrophils (polymorphonuclear leukocytes; PMN). Unstimulated PMN contained IL-1ra protein in the absence of IL-1ra mRNA; IL-1 beta mRNA and protein were undetectable. Lipopolysaccharide (LPS), granulocyte/macrophage colony-stimulating factor (GM-CSF), and tumor necrosis factor-alpha (TNF-alpha), individually, transiently increased IL-1ra steady-state mRNA levels in PMN, with associated increases in IL-1ra protein synthesis. LPS, GM-CSF, and TNF-alpha generated similar increases in IL-1 beta mRNA, yet only LPS resulted in detectable synthesis of IL-1 beta protein. IL-4 enhanced LPS-induced IL-1ra production by PMN and inhibited LPS-induced IL-1 beta production. by PMN and inhibited LPS-induced IL-1 beta production. IL-1ra protein present within stimulated PMN supernatants existed in the 22- to 25-kD glycosylated form. Polymerase chain reaction amplification determined that only sIL-1ra mRNA was present within stimulated PMN; icIL-1ra mRNA was undetectable. These results indicate that freshly isolated PMN possess a small amount of IL-1ra protein and that these cells can respond to stimuli with a low level of sIL-1ra transcription and translation. PMN may be a major source of IL-1ra in inflammatory exudates where these cells predominate.
authors.affiliation: Department of Medicine, University of Colorado Health Sciences Center, Denver 80262.
authors.forename: M
authors.initials: M
authors.lastname: Malyak
authors.forename: M F
authors.initials: MF
authors.lastname: Smith
authors.forename: A A
authors.initials: AA
authors.lastname: Abel
authors.forename: W P
authors.initials: WP
authors.lastname: Arend
mesh_terms: D001483:Base Sequence; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology; D017931:DNA Primers; D006031:Glycosylation; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000096:biosynthesis*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors*; D012795:Sialoglycoproteins / Q000096:biosynthesis*
chemical_list: D016207:Cytokines; D017931:DNA Primers; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D017472:Receptors, Interleukin-1; D012795:Sialoglycoproteins