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Communications to the Editor |

The Role of Nuclear Factor-κB Activation in Airway Inflammation Following Adenovirus Infection and COPD FREE TO VIEW

Shinji Teramoto, MD, FCCP; Haruki Kume, MD
Author and Funding Information

International University of Health and Welfare San-no Hospital Tokyo, Japan

Correspondence to: Shinji Teramoto, MD, FCCP, Department of Internal Medicine, San-no Hospital, 8–10–16 Akasaka, Minato-ku Tokyo 107-0052, Japan; e-mail: Shinjit-tky@umin.ac.jp



Chest. 2001;119(4):1294-1295. doi:10.1378/chest.119.4.1294
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To the Editor:

With great interest, we read the fine article by Christman and coworkers1 concerning the role of nuclear factor-κB (NF-κB) in pulmonary diseases.

The authors have comprehensively summarized that NF-κB regulates production of inflammatory mediators in a variety of cells and animal models. Furthermore, they showed the clinical evidence of the association of NF-κB activation with the pathogenesis of several inflammatory disorders, including ARDS, systemic inflammatory response syndrome, and bronchial asthma. However, they did not discuss the roles of NF-κB in the pathogenesis of COPD, which is also characterized by airway inflammation.

Epidemiologic studies2have implicated childhood respiratory infection as an independent risk factor for the subsequent development of persistent asthma and COPD. Adenoviruses appear to persist as latent infection in the airways of patients with COPD and adenoviral E1A proteins capable of activating host transcription factors and amplifying host gene expression, including those involved in cigarette smoke-induced lung inflammation and COPD.34 In in vitro experiments, E1A-transfected airway epithelial cells after lipopolysaccharide (LPS) exposure produce an excess amount of inflammatory cytokines interleukin (IL)-8 and intercellular adhesion molecule (ICAM)-1, but do not produce IL-1, IL-6, and granulocyte macrophage colony stimulating factor.6 Although tumor necrosis factor (TNF)-α and phorbol-myristate-acetate could induce NF-κB binding complexes of RelA and p50 in airway cells with or without E1A transection, LPS could induce nuclear translocation of NF-κB in E1A-transfected cells alone.7In E1A-transformed airway cells, the NF-κB transcription factor is involved in the IL-8 gene and ICAM-1 gene expression after LPS stimulation. In addition, Metcalf8reported that adenovirus E1A 13S gene product upregulates TNF-α gene. On the other hand, cigarette smokers have increased numbers of neutrophils present in their lower respiratory tract. Acute exposure to cigarette smoke induces infiltration of neutrophils into the airways through NF-κB and IL-8 gene expression.9 Consequently, the latent adenovirus infection and cigarette smoke synergistically cause chronic airway inflammation through the cytokine genes and adhesion molecule genes expression, possibly via NF-κB activation. Thus, NF-κB activation may be involved in the pathogenesis of COPD and chronic airway inflammation after chronic cigarette smoke inhalation and adenovirus infection. These experimental data should be further confirmed in the future by clinical data in humans.

References

Christman, JW, Sadikot, RT, Blackwell, TS (2000) The role of nuclear factor-κB in pulmonary diseases.Chest117,1482-1487. [CrossRef] [PubMed]
 
Hogg, JC Childhood viral infection and the pathogenesis of asthma and chronic obstructive pulmonary disease.Am J Respir Crit Care Med1999;160,S26-S28. [PubMed]
 
Matsuse, T, Hayashi, S, Kuwano, K, et al Latent adenoviral infection in the pathogenesis of chronic airways obstructions.Am Rev Respir Dis1992;146,177-184. [PubMed]
 
Elliott, WM, Hayashi, S, Hogg, JC Immunodetection of adenoviral E1A proteins in human lung tissues.Am J Respir Cell Mol Biol1995;12,642-648. [PubMed]
 
Keicho, N, Elliott, WM, Hogg, JC, et al Adenoviral E1A upregulates interleukin-8 expression induced by endotoxin in pulmonary epithelial cells.Am J Physiol1997;272,L1046-L1052. [PubMed]
 
Keicho, N, Elliott, WM, Hogg, JC, et al Adenoviral E1A gene dysregulates ICAM-1 expression in transformed pulmonary epithelial cells.Am J Respir Cell Mol Biol1997;16,23-30. [PubMed]
 
Keicho, N, Higashimoto, Y, Bondy, GP, et al Endotoxin-specific NF-κB activation in pulmonary epithelial cells harboring adenovirus E1A.Am J Physiol1999;277,L523-L532. [PubMed]
 
Metcalf, JP Adenovirus E1A 13S gene product upregulates tumor necrosis factor gene.Am J Physiol1996;270,L535-L540. [PubMed]
 
Nishikawa, M, Kakemizu, N, Ito, N, et al Superoxide mediates cigarette smoke-induced infiltration of neutrophils into the airways through nuclear factor-κB activation and IL-8 mRNA expression in guinea pigsin vivo.Am J Respir Cell Mol Biol1999;21,189-198
 

Figures

Tables

References

Christman, JW, Sadikot, RT, Blackwell, TS (2000) The role of nuclear factor-κB in pulmonary diseases.Chest117,1482-1487. [CrossRef] [PubMed]
 
Hogg, JC Childhood viral infection and the pathogenesis of asthma and chronic obstructive pulmonary disease.Am J Respir Crit Care Med1999;160,S26-S28. [PubMed]
 
Matsuse, T, Hayashi, S, Kuwano, K, et al Latent adenoviral infection in the pathogenesis of chronic airways obstructions.Am Rev Respir Dis1992;146,177-184. [PubMed]
 
Elliott, WM, Hayashi, S, Hogg, JC Immunodetection of adenoviral E1A proteins in human lung tissues.Am J Respir Cell Mol Biol1995;12,642-648. [PubMed]
 
Keicho, N, Elliott, WM, Hogg, JC, et al Adenoviral E1A upregulates interleukin-8 expression induced by endotoxin in pulmonary epithelial cells.Am J Physiol1997;272,L1046-L1052. [PubMed]
 
Keicho, N, Elliott, WM, Hogg, JC, et al Adenoviral E1A gene dysregulates ICAM-1 expression in transformed pulmonary epithelial cells.Am J Respir Cell Mol Biol1997;16,23-30. [PubMed]
 
Keicho, N, Higashimoto, Y, Bondy, GP, et al Endotoxin-specific NF-κB activation in pulmonary epithelial cells harboring adenovirus E1A.Am J Physiol1999;277,L523-L532. [PubMed]
 
Metcalf, JP Adenovirus E1A 13S gene product upregulates tumor necrosis factor gene.Am J Physiol1996;270,L535-L540. [PubMed]
 
Nishikawa, M, Kakemizu, N, Ito, N, et al Superoxide mediates cigarette smoke-induced infiltration of neutrophils into the airways through nuclear factor-κB activation and IL-8 mRNA expression in guinea pigsin vivo.Am J Respir Cell Mol Biol1999;21,189-198
 
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