title: Nitric oxide-dependent regulation of pro-inflammatory cytokines in group B streptococcal inflammation of rat lung.
abstract: Group B Streptococcus (GBS) infection leading to sepsis and lung injury is a major cause of neonatal morbidity and mortality. Lung injury may result from overproduction of pro-inflammatory mediators (cytokines), caused by nitric oxide (NO). Our objective was to characterize the molecular signaling events involving the pro-inflammatory mediators interleukin-6 (IL-6) and macrophage inflammatory protein (MIP-2) in the presence of aminoguanidine (AG), an inducible nitric oxide synthase (iNOS) specific inhibitor, in lung tissue from GBS-treated young rats. Changes in iNOS mRNA, lactic acid, and rectal temperature were determined as markers of the inflammatory response. Expression and regulation of IL-6 and MIP-2 mRNA in lung tissue were studied by RT-PCR with densitometry analysis. GBS treatment of young rats induced the expression of pro-inflammatory mediators IL-6 (6-fold) and MIP-2 (3-fold) in lung tissue compared to controls. AG decreased IL-6 and MIP-2 expression. Addition of L-arginine (L-arg) reversed the AG effect on IL-6 and MIP-2 expression. These data suggest a role for the nitric oxide pathway in the overproduction of pro-inflammatory mediators IL-6 and MIP-2 during GBS-induced lung inflammation. This pathway may be responsible for the initiation of lung injury.
authors.affiliation: Department of Pediatrics, Children's Hospital of Michigan, Wayne State University, Detroit, Michigan 48201, USA.
authors.forename: Vania D
authors.initials: VD
authors.lastname: Raykova
authors.forename: Maria
authors.initials: M
authors.lastname: Glibetic
authors.forename: John P
authors.initials: JP
authors.lastname: Ofenstein
authors.forename: Jacob V
authors.initials: JV
authors.lastname: Aranda
mesh_terms: D000818:Animals; D001120:Arginine / Q000494:pharmacology; D054426:Chemokine CXCL2; D019743:Chemokines, CXC; D015870:Gene Expression / Q000276:immunology; D006146:Guanidines / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008666:Metalloendopeptidases / Q000378:metabolism; D015846:Monokines / Q000235:genetics / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D016877:Oxidants / Q000378:metabolism; D011014:Pneumonia / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000276:immunology / Q000378:metabolism; D013290:Streptococcal Infections / Q000276:immunology* / Q000378:metabolism; D013292:Streptococcus agalactiae
chemical_list: D054426:Chemokine CXCL2; D019743:Chemokines, CXC; C513296:Cxcl2 protein, rat; D006146:Guanidines; D036341:Intercellular Signaling Peptides and Proteins; D015850:Interleukin-6; D015846:Monokines; D016877:Oxidants; D012333:RNA, Messenger; D009569:Nitric Oxide; D001120:Arginine; D008666:Metalloendopeptidases; C004479:pimagedine