Spironolactone inhibits production of proinflammatory mediators in response to lipopolysaccharide via inactivation of nuclear factor-κB.
The effect of spironolactone (SPIR) on lipopolysaccharide (LPS)-induced production of proinflammatory mediators was examined using RAW 264.7 macrophage-like cells and mouse peritoneal macrophages. SPIR significantly inhibited LPS-induced production of nitric oxide (NO), tumor necrosis factor-α and prostaglandin E2. The inhibition was not mediated by cell death. SPIR reduced the expression of an inducible NO synthase mRNA in response to LPS. SPIR significantly inhibited phosphorylation of p65 nuclear factor (NF)-κB in response to LPS. Furthermore, SPIR inhibited phosphorylation of IκB kinase (IKK) as an upstream molecule of NF-κB in response to LPS. LPS did not induce the production of aldosterone in RAW 264.7 cells. Taken together, SPIR is suggested to inhibit LPS-induced proinflammatory mediators via inactivation of IKK/NF-κB in LPS signaling.
Division of Diabetes, Department of Internal Medicine, Diabetes Center , Nagakute , Japan .
Yoshiro
Y
Kato
Hideki
H
Kamiya
Naoki
N
Koide
Erdenezaya
E
Odkhuu
Takayuki
T
Komatsu
Jargalsaikhan
J
Dagvadorj
Atsuko
A
Watarai
Masaki
M
Kondo
Koichi
K
Kato
Jiro
J
Nakamura
Takashi
T
Yokochi
D000450:Aldosterone / Q000096:biosynthesis; D000818:Animals; D002478:Cells, Cultured; D015232:Dinoprostone / Q000096:biosynthesis; D051550:I-kappa B Kinase / Q000378:metabolism; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D009569:Nitric Oxide / Q000096:biosynthesis; D010766:Phosphorylation; D013148:Spironolactone / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D013148:Spironolactone; D009569:Nitric Oxide; D000450:Aldosterone; D051550:I-kappa B Kinase; D015232:Dinoprostone
IκB kinase; NF-κB; lipopolysaccharide; nitric oxide; prostaglandin E2; spironolactone; tumor necrosis factor-α