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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：

PURPOSE: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.

journal_name

J Clin Immunol

journal_title

Journal of clinical immunology

authors

Wang HW,Yang W,Lu JY,Li F,Sun JZ,Zhang W,Guo NN,Gao L,Kang JR

doi

10.1007/s10875-012-9852-3

subject

Has Abstract

pub_date

2013-04-01 00:00:00

pages

649-60

issue

eissn

0271-9142

issn

1573-2592

journal_volume

pub_type

杂志文章

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N-acetylcysteine administration is associated with reduced activation of NF-kB and preserves lung dendritic cells function in a zymosan-induced generalized inflammation model.