Rhinovirus stimulation of interleukin-8 in vivo and in vitro: role of NF-kappa B

被引:132
作者
Zhu, Z
Tang, WL
Gwaltney, JM
Wu, Y
Elias, JA
机构
[1] YALE UNIV, SCH MED, DEPT INTERNAL MED, PULM & CRIT CARE MED SECT, NEW HAVEN, CT 06520 USA
[2] UNIV VIRGINIA, HLTH SCI CTR, DEPT INTERNAL MED, DIV EPIDEMIOL & VIROL, CHARLOTTESVILLE, VA 22908 USA
关键词
nuclear factor-kappa B; nose; epithelial cell; airway;
D O I
10.1152/ajplung.1997.273.4.L814
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
Neutrophil infiltration is a well-documented early event in the pathogenesis of rhinovirus (RV) infections. To further understand the mechanisms responsible for this neutrophilia, we determined whether interleukin (IL)-8 was present at sites of experimental RV infection in vivo and characterized the mechanism(s) by which RV stimulates IL-8 production in vitro. IL-8 was readily detectable in the nasal washings of all normal volunteers and did not increase with sham nasal inoculation. In contrast, RV infection caused a significant additional increase in nasal IL-8, the levels of which peaked 48-72 h after virus inoculation. RV was a potent stimulator of IL-8 protein production by A549 epithelial-like cells, MRC-5 fibroblasts, and normal human bronchial epithelial cells in vitro. This induction was associated with a significant increase in IL-8 mRNA accumulation and gene transcription. RV also stimulated IL-8 promoter-driven luciferase activity. This stimulation was significantly decreased by mutation of the nuclear factor (NF)-IL-6 site and was completely abrogated by mutation of the NF-kappa B site in this promoter. In addition, NF-kappa B-DNA binding activity was rapidly induced in RV-infected cells. This inducible binding was made up of p65 and, to a lesser extent, p50 NF-kappa B moieties. These studies demonstrate that IL-8 is present in normal nasal secretions and that the levels of IL-8 are further increased after RV infection. They also demonstrate that RVs are potent stimulators of IL-8 production and that this induction is mediated, at least in part, by an NF-kappa B-dependent transcriptional activation pathway. IL-8 may contribute to the pathogenesis of RV infection, and NF-kappa B activation may be a central event in RV-induced pathologies.
引用
收藏
页码:L814 / L824
页数:11
相关论文
共 45 条
[1]   NF-kappa B: Ten years after [J].
Baeuerle, PA ;
Baltimore, D .
CELL, 1996, 87 (01) :13-20
[2]   INTERLEUKIN-8 EXPRESSION IN NORMAL NASAL EPITHELIUM AND ITS MODULATION BY INFECTION WITH RESPIRATORY SYNCYTIAL VIRUS AND CYTOKINES TUMOR-NECROSIS-FACTOR, INTERLEUKIN-1, AND INTERLEUKIN-6 [J].
BECKER, S ;
KOREN, HS ;
HENKE, DC .
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, 1993, 8 (01) :20-27
[3]   A COMMON COLD VIRUS, RHINOVIRUS-16, POTENTIATES AIRWAY INFLAMMATION AFTER SEGMENTAL ANTIGEN BRONCHOPROVOCATION IN ALLERGIC SUBJECTS [J].
CALHOUN, WJ ;
DICK, EC ;
SCHWARTZ, LB ;
BUSSE, WW .
JOURNAL OF CLINICAL INVESTIGATION, 1994, 94 (06) :2200-2208
[4]   SINGLE-STEP METHOD OF RNA ISOLATION BY ACID GUANIDINIUM THIOCYANATE PHENOL CHLOROFORM EXTRACTION [J].
CHOMCZYNSKI, P ;
SACCHI, N .
ANALYTICAL BIOCHEMISTRY, 1987, 162 (01) :156-159
[5]  
COUCH RB, 1990, VIROLOGY, P607
[6]  
DAMME JV, 1994, CYTOKINE HDB, P185
[7]  
Douglas R G Jr, 1968, Antimicrob Agents Chemother (Bethesda), V8, P340
[8]   REQUIREMENT FOR NUCLEAR FACTOR (NF)-KAPPA-B P65 AND NF-INTERLEUKIN-6 BINDING-ELEMENTS IN THE TUMOR-NECROSIS-FACTOR RESPONSE REGION OF THE GRANULOCYTE-COLONY-STIMULATING FACTOR PROMOTER [J].
DUNN, SM ;
COLES, LS ;
LANG, RK ;
GERONDAKIS, S ;
VADAS, MA ;
SHANNON, MF .
BLOOD, 1994, 83 (09) :2469-2479
[9]  
ELIAS JA, 1994, J IMMUNOL, V152, P2421
[10]  
EUSTICE DC, 1991, BIOTECHNIQUES, V11, P739