Respiratory syncytial virus-induced activation of nuclear factor-κB in the lung involves alveolar macrophages and toll-like receptor 4-dependent pathways

被引:192
作者
Haeberle, HA
Takizawa, R
Casola, A
Brasier, AR
Dieterich, HJ
van Rooijen, N
Gatalica, Z
Garofalo, RP
机构
[1] Univ Texas, Dept Pediat, Med Branch, Galveston, TX 77555 USA
[2] Univ Texas, Dept Med, Med Branch, Galveston, TX 77555 USA
[3] Univ Texas, Dept Microbiol & Immunol, Med Branch, Galveston, TX 77555 USA
[4] Vrije Univ Amsterdam, Dept Cell Biol & Immunol, Amsterdam, Netherlands
[5] Univ Klinikum Tubingen, Dept Anesthesiol, Tubingen, Germany
[6] Univ Texas, Dept Pathol, Med Branch, Galveston, TX 77555 USA
关键词
D O I
10.1086/344644
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The transcription factor nuclear factor (NF)-kappaB controls the expression of numerous respiratory syncytial virus (RSV)-inducible inflammatory and immunomodulatory genes. Using a BALB/c mouse model, the present article shows that RSV potently and specifically activates NF-kappaB in vivo, a process that involves nuclear translocation of the subunits RelA, p50, and c-Rel in the lung. By depletion of alveolar macrophages (AMs) in BALB/c mice and use of C3H/HeJ mice lacking a functional Toll-like receptor (TLR)-4 signaling pathway, we demonstrate the existence of distinct but sequentially integrated RSV-inducible early NF-kappaB responses in the lung. The first response occurs early after RSV inoculation, is AM and TLR4 dependent, and is viral replication independent, whereas the second response involves epithelial cells and/or inflammatory cells, is TLR4 independent, and requires viral replication. NF-kappaB may be considered a central activator of not only inflammatory but also innate immune responses to RSV.
引用
收藏
页码:1199 / 1206
页数:8
相关论文
共 51 条
[1]   Toll-like receptors in the induction of the innate immune response [J].
Aderem, A ;
Ulevitch, RJ .
NATURE, 2000, 406 (6797) :782-787
[2]   Toll-like receptors: critical proteins linking innate and acquired immunity [J].
Akira, S ;
Takeda, K ;
Kaisho, T .
NATURE IMMUNOLOGY, 2001, 2 (08) :675-680
[3]   Mechanisms of disease - Nuclear factor-kappa b - A pivotal transcription factor in chronic inflammatory diseases [J].
Barnes, PJ ;
Larin, M .
NEW ENGLAND JOURNAL OF MEDICINE, 1997, 336 (15) :1066-1071
[4]  
BECKER S, 1991, J IMMUNOL, V147, P4307
[5]   THE I-KAPPA-B PROTEINS - MULTIFUNCTIONAL REGULATORS OF REL/NF-KAPPA-B TRANSCRIPTION FACTORS [J].
BEG, AA ;
BALDWIN, AS .
GENES & DEVELOPMENT, 1993, 7 (11) :2064-2070
[6]   DEPLETION OF ALVEOLAR MACROPHAGES BY LIPOSOME-ENCAPSULATED DICHLOROMETHYLENE DIPHOSPHONATE [J].
BERG, JT ;
LEE, ST ;
THEPEN, T ;
LEE, CY ;
TSAN, MF .
JOURNAL OF APPLIED PHYSIOLOGY, 1993, 74 (06) :2812-2819
[7]   Transcriptional induction of multiple cytokines by human respiratory syncytial virus requires activation of NF-kappa B and is inhibited by sodium salicylate and aspirin [J].
Bitko, V ;
Velazquez, A ;
Yang, L ;
Yang, YC ;
Barik, S .
VIROLOGY, 1997, 232 (02) :369-378
[8]   Role of NF kappa B in the mortality of sepsis [J].
Bohrer, H ;
Qiu, F ;
Zimmerman, T ;
Zhang, YM ;
Jllmer, T ;
Mannel, D ;
Bottiger, BW ;
Stern, DM ;
Waldherr, R ;
Saeger, HD ;
Ziegler, R ;
Bierhaus, A ;
Martin, E ;
Nawroth, PP .
JOURNAL OF CLINICAL INVESTIGATION, 1997, 100 (05) :972-985
[9]   Multiple cis regulatory elements control RANTES promoter activity in alveolar epithelial cells infected with respiratory syncytial virus [J].
Casola, A ;
Garofalo, RP ;
Haeberle, H ;
Elliott, TF ;
Lin, RT ;
Jamaluddin, M ;
Brasier, AR .
JOURNAL OF VIROLOGY, 2001, 75 (14) :6428-6439
[10]   Inhibition of viral replication reverses respiratory syncytial virus-induced NF-kappa B activation and interleukin-8 gene expression in A549 cells [J].
Fiedler, MA ;
WernkeDollries, K ;
Stark, JM .
JOURNAL OF VIROLOGY, 1996, 70 (12) :9079-9082