Lipopolysaccharide induction of MARCKS-related protein and cytokine secretion are differentially impaired in microglia from LPS-nonresponsive (C3H/HeJ) mice.
Many events involved in activation of microglia and leukocytes by lipopolysaccharide (LPS) are mediated by protein kinase C (PKC), and we have recently demonstrated that a major PKC substrate, MARCKS-related protein (MRP), is selectively induced by LPS in murine microglia. In microglia from LPS-nonresponsive (C3H/HeJ) mice, induction of MRP and secretion of CSF-1 required much higher LPS concentrations (> or = 100 ng/ml) than in normal (C3H/OuJ) microglia (< or = 10 ng/ml). By contrast, TNF alpha production was not significantly increased in C3H/HeJ microglia even at 1 microgram LPS/ml. Microglia expressed PKC isoforms alpha, beta, delta, and zeta (but not gamma and epsilon); PKC isoform levels were similar in both normal and C3H/HeJ microglia and no significant change in response to LPS was noted. Our results indicate that LPS alters PKC substrate (rather than kinase) expression, and that the Lpsd mutation in C3H/HeJ mice differentially affects regulation of several gene products implicated in microglial function.
Byers
D M
DM
Department of Pediatrics, Dalhousie University, Halifax, Nova Scotia, Canada. David.Byers@Dal.Ca
Rosé
S D
SD
Cook
H W
HW
Hao
C
C
Fedoroff
S
S
D000818:Animals; D015153:Blotting, Western; D002148:Calmodulin-Binding Proteins; D002478:Cells, Cultured; D003115:Colony-Stimulating Factors / Q000096:biosynthesis; D016207:Cytokines / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D047908:Intracellular Signaling Peptides and Proteins; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008565:Membrane Proteins / Q000096:biosynthesis*; D051379:Mice; D008815:Mice, Inbred Strains; D008840:Microfilament Proteins; D017628:Microglia / Q000378:metabolism*; D009154:Mutation; D000076250:Myristoylated Alanine-Rich C Kinase Substrate; D014176:Protein Biosynthesis; D011493:Protein Kinase C; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D002148:Calmodulin-Binding Proteins; D003115:Colony-Stimulating Factors; D016207:Cytokines; D047908:Intracellular Signaling Peptides and Proteins; D008070:Lipopolysaccharides; C000619711:Marcks protein, mouse; C512945:Marcksl1 protein, mouse; D008565:Membrane Proteins; D008840:Microfilament Proteins; D014409:Tumor Necrosis Factor-alpha; D000076250:Myristoylated Alanine-Rich C Kinase Substrate; D011493:Protein Kinase C