Secretion of IL-1: role of protein kinase C.
In an attempt to define the mechanism by which endotoxin induces its biologic activity, LPS was incorporated into phospholipid vesicles (liposomes) and compared with free LPS for ability to stimulate human monocytes. Activation of human monocytes by free LPS caused the translocation of protein kinase C (PKC) from the cytosol to the plasma membranes, the production of both IL-1, alpha and beta, and IL-1 secretion. Activation by LPS presented in multilamellar vesicles (MLV)-LPS caused IL-1 production but not IL-1 secretion. Moreover, MLV-LPS did not induce PKC translocation. MLV themselves did not inhibit monocyte stimulation by LPS, since LPS presented at the surface of lyophilized liposomes behaved like free LPS in cell activation. In contrast, MLV-LPS primed monocytes for subsequent LPS stimulation. When monocytes were activated by LPS in the presence of PKC inhibitors, no plasma membrane-associated PKC or IL-1 secretion was detected, whereas IL-1 production was observed. PKC inhibitors did not affect IL-1 alpha and IL-1 beta production, showing that PKC is not involved in the production of either IL-1. It can be concluded that IL-1 production and secretion are induced independently, and that IL-1 secretion involves PKC.
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
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000470:Alkaloids / Q000494:pharmacology; D001692:Biological Transport; D002451:Cell Compartmentation; D002462:Cell Membrane / Q000201:enzymology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000378:metabolism*; D007527:Isoenzymes / Q000502:physiology; D007546:Isoquinolines / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000008:administration & dosage; D008081:Liposomes; D009000:Monocytes / Q000378:metabolism*; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology*; D019311:Staurosporine
D000470:Alkaloids; D007375:Interleukin-1; D007527:Isoenzymes; D007546:Isoquinolines; D008070:Lipopolysaccharides; D008081:Liposomes; D010879:Piperazines; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D011493:Protein Kinase C; D019311:Staurosporine