Induction of IL-1: independent production of IL-1 alpha and IL-1 beta.
Lipopolysaccharide (LPS) either in its soluble form or associated with multilamellar phospholipid vesicles (liposomes) was investigated for its ability to induce human monocyte interleukin (IL)-1 alpha and IL-1 beta. When human monocytes were activated in vitro by LPS either in its soluble form or presented at the surface of lyophilized multilamellar vesicles (Lyo-MLV-LPS), both IL-1 alpha and IL-1 beta were detected intracellularly and extracellularly, using specific antisera. In correlation with these findings, the mRNAs for IL-1 alpha and IL-1 beta were both found by Northern blot analysis. However, when human monocytes were stimulated by LPS incorporated into multilamellar vesicles which had not been previously lyophilized, a different pattern of IL-1 protein and message was observed. IL-1 alpha activity was detected only intracellularly and not in the supernatant, while IL-1 beta was not produced at all. Northern blotting revealed only mRNA for IL-1 alpha as soon as 0.5 h after stimulation and none for IL-1 beta. These data indicate independent induction of IL-1 alpha and IL-1 beta. Moreover, it appears that the regulation occurs at the transcriptional level, since with MLV-LPS only the mRNA for IL-1 alpha was induced. The lack of IL-1 beta could be due to either a blockage at the DNA level, an undetectable level of IL-1 beta mRNA, or a very short halflife for IL-1 beta mRNA. These findings indicate that although IL-1 alpha and IL-1 beta may have identical biological properties and share the same receptor, their induction and secretion are regulated by independent pathways.(ABSTRACT TRUNCATED AT 250 WORDS)
Bakouche
O
O
University of Texas M.D. Anderson Cancer Center, Department of Cell Biology, Houston 77030.
Moreau
J L
JL
Lachman
L B
LB
D000818:Animals; D015152:Blotting, Northern; D002460:Cell Line; D002462:Cell Membrane / Q000502:physiology; D003600:Cytosol / Q000502:physiology; D004247:DNA / Q000302:isolation & purification; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity*; D051379:Mice; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D009693:Nucleic Acid Hybridization; D012313:RNA / Q000302:isolation & purification
D007375:Interleukin-1; D008070:Lipopolysaccharides; D012313:RNA; D004247:DNA