title: Human monocyte ATP-induced IL-1 beta posttranslational processing is a dynamic process dependent on in vitro growth conditions.
abstract: Despite a large production capacity, freshly isolated lipopolysaccharide (LPS)-activated human monocytes release only a small percentage of their newly synthesized interleukin (IL)-1 beta into the medium. Extracellular ATP, acting via surface P2z-type purino-receptors, increases cytokine posttranslational processing. To explore whether this ATP response was affected by culture conditions, monocytes were maintained for different time periods in the absence and presence of various media components including fetal bovine and human sera and recombinant human cytokines. The ability of monocytes to produce radiolabeled pro-IL-1 beta in response to LPS and to posttranslationally process the procytokine after ATP stimulation was affected both by time in culture and by the presence of specific media components. These observations indicate that ATP's ability to promote human monocyte IL-1 beta posttranslational processing is a dynamic process that is subject to regulation by cytokines and/or growth factors. Changes in monocyte/macrophage ATP responsiveness may provide an important regulatory mechanism for the control of IL-1 biological activity in vivo.
authors.affiliation: Department of Cancer, Immunology, and Infectious Diseases, Pfizer Inc., Groton, Connecticut 06340, USA.
authors.forename: R E
authors.initials: RE
authors.lastname: Laliberte
authors.forename: D G
authors.initials: DG
authors.lastname: Perregaux
authors.forename: P
authors.initials: P
authors.lastname: McNiff
authors.forename: C A
authors.initials: CA
authors.lastname: Gabel
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D001681:Biological Assay; D002478:Cells, Cultured; D016922:Cellular Senescence; D003470:Culture Media; D006593:Hexokinase / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D009000:Monocytes / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D012795:Sialoglycoproteins / Q000378:metabolism
chemical_list: D003470:Culture Media; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D012795:Sialoglycoproteins; D007371:Interferon-gamma; D000255:Adenosine Triphosphate; D006593:Hexokinase