TY  - JOUR
AU  - Lappas, M
AU  - Permezel, M
AU  - Rice, GE
Y2  - 2014/05/21
Y1  - 2003/04/01
SN  - 0021-972X
UR  - http://hdl.handle.net/11343/26476
AB  - The production of reactive oxygen species (ROS), prostaglandins (PGs), proinflammatory cytokines, and proteases has been implicated in the pathogenesis of term and preterm labor. The nuclear factor-kappaB (NF-kappaB) transcription pathway is activated by ROS and is a key regulator of PGs, proinflammatory cytokine release, and protease activity. N-Acetyl-cysteine (NAC) is an antioxidant that through its ability to scavenger ROS suppresses NF-kappaB DNA-binding activity and resultant gene expression. The aim of this study was to elucidate the effect of NAC on NF-kappaB DNA-binding activity, phospholipid metabolism, cytokine release, and protease activity from human fetal membranes. Human amnion and choriodecidua (n = 9 separate placentas) were treated with 0 (control), 5, 10, or 15 mM NAC in the presence of 10 micro g/ml lipopolysaccharide. After 6-h incubation, the tissues were collected, NF-kappaB DNA binding activity was assessed by gel shift binding assays, and matrix metalloproteinase-9 and urokinase-type plasminogen activator activity were determined by zymography. The incubation medium was collected and assayed for type II phospholipase A(2) tissue content, IL-6, IL-8, TNFalpha, and 8-isoprostane release by ELISA. The release of PGF(2alpha) was measured by RIA. Treatment of fetal membranes with NAC significantly suppressed lipopolysaccharide-stimulated type II phospholipase A(2) release and content; PGF(2alpha), IL-6, IL-8, TNFalpha, and 8-isoprostane release; and matrix metalloproteinase-9 and urokinase-type plasminogen activator enzyme activity and suppressed NF-kappaB DNA-binding activity (by ANOVA, P < 0.05). The data presented in this study demonstrate that NAC inhibits an NF-kappaB-activated pathway and subsequent phospholipid metabolism, proinflammatory cytokine release, and protease activity in human fetal membranes.
N1  - application/pdf
LA  - English
PB  - ENDOCRINE SOC
KW  - Obstetrics and Gynaecology ; Endocrine Organs and Diseases (incl. Diabetes)
T1  - N-acetyl-cysteine inhibits phospholipid metabolism, proinflammatory cytokine release, protease activity, and nuclear factor-kappa B deoxyribonucleic acid-binding activity in human fetal membranes in vitro
DO  - 10.1210/jc.2002-021677
IS  - JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
VL  - 88
IS  - 4
SP  - 1723-1729
L1  - /bitstream/handle/11343/26476/116272_5322.pdf?sequence=1&isAllowed=n
ER  -