Nuclear factor-kappa B expression in alveolar macrophages of mechanically ventilated neonates with respiratory distress syndrome

被引:28
作者
Cao, L
Liu, CQ
Cai, BP
Jia, XQ
Kang, LM
Speer, CP
Sun, B
机构
[1] Hebei Prov Peoples Hosp, Dept Pediat, Shijiazhuang, Peoples R China
[2] Childrens Hosp Hebei Prov, Serv Neonatol, Shijiazhuang, Peoples R China
[3] Univ Childrens Hosp, Wurzburg, Germany
[4] Fudan Univ, Childrens Hosp, Dept Pediat, Lab Resp & Intens Care Med, Shanghai 200032, Peoples R China
来源
BIOLOGY OF THE NEONATE | 2004年 / 86卷 / 02期
关键词
alveolar macrophage; interleukin-1; beta; interleukin-8; nuclear factor-kappa B; nuclear factor-kappa B inhibitor; respiratory distress syndrome;
D O I
10.1159/000078940
中图分类号
R72 [儿科学];
学科分类号
100202 ;
摘要
Background: Inflammatory reaction and injury in mature lungs are associated with activation of nuclear factor-kappaB (NF-kappaB) to trigger proinflammatory cytokine release. In preterm infants with immature lungs, this mechanism is not yet fully understood, therefore we investigated this mechanism in mechanically ventilated neonates with respiratory distress syndrome (RDS). Methods: Serial samples of the airway aspirates (AA) were obtained during mechanical ventilation from 21 preterm infants with RDS, of which 12 were survivors (birth weight 1.48 +/- 0.32 kg and gestational age 31 +/- 1.5 weeks) and 9 nonsurvivors (1.34 +/- 0.31 kg and 30 +/- 2 weeks). Seven neonates matched for age and birth weight without respiratory disorders served as controls. Alveolar macrophages (AM) of AA were isolated by differential adherence, some were cultured with lipopolysaccharide (LPS) for 1 h. Then, nuclear extracts of AM were analyzed by electrophoretic mobility shift assay for NF-kappaB expression. The NF-kappaB inhibitor (IkappaB-alpha protein) in cytoplasmic extracts was detected by Western blot, and concentrations of IL-1 and IL-8 in AA by enzyme-linked immunosorbent assay (ELISA). Results: On day 2 NF-kappaB expression in AM was significantly increased in the survivors and nonsurvivors at 33.3 +/- 9 and 54.8 +/- 10.2 relative density units (RDU) compared to control infants (11.1 +/- 6.7; p < 0.01). Expression of I kappa B-alpha was significantly higher in controls than that in the survivors and nonsurvivors on days 2 and 4. Moreover, in the nonsurvivors of RDS, expression of NF-kappa B was decreased following LPS stimulation in vitro on day 4. IL-1 and IL-8 levels in the AA supernatant were higher in the survivors than in controls on days 2 and 4, but lower than those of the nonsurvivors on day 2. There were close correlations between the expression of NF-kappa B and levels of IL-1 (r = 0.78, p < 0.01), and IL-8 (r = 0.81, p < 0.01) in AA. Conclusion: There were alterations in NF-kappa B activity in the AM of mechanically ventilated preterm neonates with RDS, mediated by decreased synthesis and increased degradation of I kappa B. Copyright (C) 2004 S. Karger AG, Basel.
引用
收藏
页码:116 / 123
页数:8
相关论文
共 27 条
  • [11] Cytokines in chronic lung disease of prematurity
    Kotecha, S
    [J]. EUROPEAN JOURNAL OF PEDIATRICS, 1996, 155 : S14 - S17
  • [12] Differential regulation of IL-8 by IL-1β and TNFα in hyaline membrane disease
    Kwong, KY
    Jones, CA
    Cayabyab, R
    Lecart, C
    Stotts, CL
    Randhawa, I
    Ramanathan, R
    Khuu, N
    Minoo, P
    [J]. JOURNAL OF CLINICAL IMMUNOLOGY, 1998, 18 (01) : 71 - 80
  • [13] Essential role of alveolar macrophages in intrapulmonary activation of NF-κB
    Lentsch, AB
    Czermak, BJ
    Bless, NM
    Van Rooijen, N
    Ward, PA
    [J]. AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, 1999, 20 (04) : 692 - 698
  • [14] CLINICAL AND BIOLOGICAL SIGNIFICANCE OF INTERLEUKIN-10 PLASMA-LEVELS IN PATIENTS WITH SEPTIC SHOCK
    MARCHANT, A
    ALEGRE, ML
    HAKIM, A
    PIERARD, G
    MARECAUX, G
    FRIEDMAN, G
    DEGROOTE, D
    KAHN, RJ
    VINCENT, JL
    GOLDMAN, M
    [J]. JOURNAL OF CLINICAL IMMUNOLOGY, 1995, 15 (05) : 266 - 273
  • [15] Recognition of bacterial endotoxin in the lungs
    Martin, TR
    [J]. AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, 2000, 23 (02) : 128 - 132
  • [16] Activation of second messenger pathways in alveolar macrophages by endotoxin
    Monick, MM
    Hunninghake, GW
    [J]. EUROPEAN RESPIRATORY JOURNAL, 2002, 20 (01) : 210 - 222
  • [17] Munshi UK, 1997, PEDIATR PULM, V24, P331
  • [18] Mucosal tumor necrosis factor-alpha production and extensive disruption of sulfated glycosaminoglycans begin within hours of birth in neonatal respiratory distress syndrome
    Murch, SH
    Costeloe, K
    Klein, NJ
    Rees, H
    McIntosh, N
    Keeling, JW
    MacDonald, TT
    [J]. PEDIATRIC RESEARCH, 1996, 40 (03) : 484 - 489
  • [19] Ozdemir A, 1997, PEDIATR PULM, V23, P292, DOI 10.1002/(SICI)1099-0496(199704)23:4<292::AID-PPUL7>3.0.CO
  • [20] 2-O