title: N-acetylcysteine administration is associated with reduced activation of NF-kB and preserves lung dendritic cells function in a zymosan-induced generalized inflammation model.
abstract: OBJECTIVE
  In severe sepsis, functional impairment and decreased numbers of dendritic cells (DCs) are essential reasons for immune function paralysis, secondary organ infection, and organ failure. We investigated the effects of N-acetylcysteine (NAC) administration on protecting lung DCs function in a zymosan-induced generalized inflammation (ZIGI) model.
  
  
  METHODS
  ZIGI was initiated in 80 Balb/c mice by intraperitoneal injection of zymosan (ZYM; 900 mg/kg). Mice were divided into 4 groups: (1) SHAM+Vehicle; (2) SHAM+NAC; (3) ZYM+Vehicle; and (4) ZYM+NAC. NAC (100 mg/kg) was administered at different time after ZYM injection. After 48 h, we assessed: lung tissue pathological changes; arterial blood gas values; purified lung DCs surface expressions of MHC-II/I-A(d) and co-stimulatory molecules CD80, CD83, and CD86; lung DCs mRNA levels of chemokine receptors CCR5 and CCR7; lung DCs apoptosis; lung DCs ultrastructure by transmission electron microscopy; lung DCs NF-kB transcription factor activity; and LPS-stimulated lung DCs in vitro production of IL-12 and IL-10 were examined.
  
  
  RESULTS
  NAC treatment resulted in: significant improvements in ZYM-induced lung tissue damage and impaired lung function; inhibited lung DCs ZYM-induced increased expression of MHC-II/I-A(d), CD83, and CD86, but not CD80; reduced lung DCs ZYM-induced CCR5 and CCR7 mRNA levels; suppressed ZYM-induced lung DCs apoptosis; ameliorated ZYM-induced lung DCs ultrastructural abnormalities; inhibited ZYM-induced lung DCs NF-κB activity; and enhanced lung DCs production of IL-12 and inhibited their production of IL-10.
  
  
  CONCLUSIONS
  Repeated injections of NAC during the early stage of severe sepsis effectively inhibited lung DCs activation and their apoptosis, which could preserve DCs function.
authors.affiliation: Department of Pathology, the First Affiliated Hospital of General Hospital of Chinese People's Liberation Army, Beijing, 100048, China.
authors.forename: Hong-Wei
authors.initials: HW
authors.lastname: Wang
authors.forename: Wen
authors.initials: W
authors.lastname: Yang
authors.forename: Jiang-Yang
authors.initials: JY
authors.lastname: Lu
authors.forename: Fei
authors.initials: F
authors.lastname: Li
authors.forename: Jun-Zhong
authors.initials: JZ
authors.lastname: Sun
authors.forename: Wen
authors.initials: W
authors.lastname: Zhang
authors.forename: Nan-Nan
authors.initials: NN
authors.lastname: Guo
authors.forename: Lei
authors.initials: L
authors.lastname: Gao
authors.forename: Jia-Rui
authors.initials: JR
authors.lastname: Kang
mesh_terms: D000111:Acetylcysteine / Q000008:administration & dosage*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology* / Q000648:ultrastructure; D004195:Disease Models, Animal; D004789:Enzyme Activation / Q000187:drug effects; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007249:Inflammation / Q000139:chemically induced / Q000276:immunology* / Q000378:metabolism* / Q000401:mortality; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D019713:Receptors, CCR5 / Q000235:genetics / Q000378:metabolism; D054400:Receptors, CCR7 / Q000235:genetics / Q000378:metabolism; D012129:Respiratory Function Tests; D015054:Zymosan / Q000009:adverse effects
chemical_list: D016207:Cytokines; D000949:Histocompatibility Antigens Class II; D016328:NF-kappa B; D012333:RNA, Messenger; D019713:Receptors, CCR5; D054400:Receptors, CCR7; D015054:Zymosan; D000111:Acetylcysteine