Down-modulation through protein kinase C-alpha of lipopolysaccharide-induced expression of membrane CD14 in mouse bone marrow granulocytes.
We have previously shown that stimulation of mouse bone marrow granulocytes (BMC) by lipopolysaccharide (LPS) induces the expression of CD14. We found here that phorbol 12-myristate 13-acetate (PMA) blocks this LPS effect. The aim of this study was to investigate the mechanism by which PMA can block the LPS signaling pathway in BMC. The unmodified binding of a radiolabeled LPS in PMA-treated cells indicated that the PMA effect was not the consequence of a shedding or an internalization of the LPS receptor, but was rather due to a biochemical event that follows the interaction of LPS with its receptor. The observations that a selective activator of protein kinase C (PKC)-alpha (sapintoxin D) mimics the PMA effect, whereas a selective PKC-alpha inhibitor (Ro-320432) antagonizes this effect, suggest a regulatory role of PKC-alpha in the LPS signaling pathway in mouse BMC.
Pedron
T
T
Molecular Immunophysiology Unit, URA-1961 of the National Center for Scientific Research, Pasteur Institute, Paris, France.
Girard
R
R
Chaby
R
R
D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D002273:Carcinogens / Q000494:pharmacology; D002478:Cells, Cultured; D015536:Down-Regulation; D004347:Drug Interactions; D004789:Enzyme Activation; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006098:Granulocytes / Q000187:drug effects* / Q000502:physiology; D007527:Isoenzymes / Q000187:drug effects / Q000502:physiology*; D018950:Lipopolysaccharide Receptors / Q000096:biosynthesis* / Q000235:genetics; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D008809:Mice, Inbred C3H; D011493:Protein Kinase C / Q000187:drug effects / Q000502:physiology*; D051571:Protein Kinase C-alpha; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D002273:Carcinogens; D007527:Isoenzymes; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; C496630:Prkca protein, mouse; D011493:Protein Kinase C; D051571:Protein Kinase C-alpha; D013755:Tetradecanoylphorbol Acetate