Prevention of endotoxin-induced lethality in mice by calmodulin kinase activator.
Porphyromonas gingivalis strain 381 lipid A showed lower activity in inducing interleukin (IL)-1alpha and IL-1beta production and cytokine mRNA expression than synthetic Escherichia coli lipid A (compound 506) in alveolar macrophages of C57BL/6 mice. Both the lipid As induced tumor necrosis factor alpha in alveolar macrophages and IL-6 in peritoneal macrophages. A calmodulin (CaM) antagonist, W-7, inhibited IL-1beta production and its mRNA expression induced by P. gingivalis lipid A but not compound 506 in alveolar macrophages. A CaM kinase activator reduced the induction of IL-1beta in the serum of mice when administered with compound 506, and protected the mice against the lethal toxicity. The modulation of a variety of intracellular enzymes including the CaM kinase may result in clinical control of endotoxic sepsis.
Asai
Y
Y
Department of Oral Microbiology, Asahi University School of Dentistry, 1851-1 Hozumi-cho, Motosu-gun, Gifu, Japan.
Uchida
H
H
Yamamoto
H
H
Ohyama
Y
Y
Jinno
T
T
Taiji
Y
Y
Ochiai
K
K
Ogawa
T
T
D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D004731:Endotoxins / Q000097:blood / Q000633:toxicity*; D020536:Enzyme Activators / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004926:Escherichia coli; D007476:Ionophores / Q000494:pharmacology; D008050:Lipid A / Q000138:chemical synthesis / Q000633:toxicity*; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016966:Porphyromonas gingivalis / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D012772:Shock, Septic / Q000401:mortality / Q000517:prevention & control*; D013449:Sulfonamides / Q000494:pharmacology
D016207:Cytokines; D004731:Endotoxins; D020536:Enzyme Activators; D004791:Enzyme Inhibitors; D007476:Ionophores; D008050:Lipid A; D013449:Sulfonamides; C017967:W 7; D011493:Protein Kinase C; D017871:Calcium-Calmodulin-Dependent Protein Kinases