Group B Streptococci and inducible nitric oxide synthase: modulation by nuclear factor kappa B and ibuprofen.
Group B Streptococci (GBS) neonatal infections cause a complex inflammatory process involving numerous biochemical mediators. Nitric Oxide (NO) is generated by many cell types in response to different inflammatory signals. Nuclear factor kappa B (NFkappaB) plays an important role in the inflammatory process and may induce a number of biochemical mediator genes, including the inducible nitric oxide synthase (iNOS). We tested the hypothesis that GBS induces iNOS gene expression through activation of NFkappaB. We also tested whether ibuprofen (IBU) will suppress iNOS expression by blocking NFkappaB activation. Cerebral microvascular endothelial cells isolated from newborn piglets were harvested for the determination of iNOS gene expression and activation of NFkappaB. GBS significantly induced iNOS mRNA expression (5- to 6-fold, P < .005) and iNOS protein (3- to 4-fold, P < .01) at 24 hours. DNA-NFkappaB binding activity was detected within 15 minutes of GBS treatment and reached a maximal effect at 3 hours. Treatment with IBU significantly suppressed GBS-induced iNOS mRNA expression at 24 hours, and NFkappaB activity at 3 hours, suggesting that suppression of GBS-induced iNOS mRNA expression by IBU occurs by blocking of NFkappaB activation. These data show that NFkappaB activation is an early step in the induction of iNOS gene expression by GBS and that this interaction may play a vital role in the pathogenesis of GBS neonatal infections.
Glibetic
M
M
Division of Clinical Pharmacology/Toxicology, Children's Hospital of Michigan, Wayne State University, Detroit 48201, USA.
Samlalsingh-Parker
J
J
Raykova
V
V
Ofenstein
J
J
Aranda
J V
JV
D000818:Animals; D004730:Endothelium, Vascular / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D007052:Ibuprofen / Q000494:pharmacology*; D007231:Infant, Newborn; D016328:NF-kappa B / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D012333:RNA, Messenger / Q000096:biosynthesis; D013290:Streptococcal Infections; D013292:Streptococcus agalactiae / Q000502:physiology*
D016328:NF-kappa B; D012333:RNA, Messenger; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D007052:Ibuprofen