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The Role of Nuclear Factor Kappa B in the Pathogenesis of Pulmonary Diseases: Implications for Therapy

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American Journal of Respiratory Medicine

Abstract

The nuclear factor kappa B (NF-κB) transcription factor plays a key role in the induction of pro-inflammatory gene expression, leading to the synthesis of cytokines, adhesion molecules, chemokines, growth factors and enzymes. Results of studies in in vitro and in vivo models of inflammation and malignancy have also suggested central roles for NF-κB in programmed cell death, or apoptosis.

NF-κB plays a central role in a variety of acute and chronic inflammatory diseases. In the common lung diseases associated with a significant inflammatory component such as severe sepsis, acute lung injury, acute respiratory distress syndrome, cystic fibrosis and asthma, the pathogenic roles of NF-κB have been extensively investigated. In COPD, activation of NF-κB has been implicated in disease pathogenesis but its exact role is less clearly demonstrable in this heterogeneous patient population. However, the principal risk factor for COPD, cigarette smoking, is strongly associated with NF-κB activation.

Activation of NF-κB has been demonstrated in mineral dust diseases and probably plays a role in the pathogenesis of these chronic illnesses. NF-kB also plays a variety of roles in lung cancer including resistance to chemotherapy, inhibition of tumorigenesis and inducing expression of antiapoptotic genes. The complex NF-κB pathway offers a variety of potential molecular targets for chemotherapeutic intervention. A variety of agents aimed at modulating NF-κB activity are in various stages of investigation.

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  1. Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, Vanderbilt University School of Medicine, USA

    Jeffrey G. Wright &  John W. Christman

  2. Department of Veterans Affairs, Nashville, Tennessee, USA

    Jeffrey G. Wright &  John W. Christman

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  1. Jeffrey G. Wright
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Correspondence to John W. Christman.

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Wright, J.G., Christman, J.W. The Role of Nuclear Factor Kappa B in the Pathogenesis of Pulmonary Diseases: Implications for Therapy. Am J Respir Med 2, 211–219 (2003). https://doi.org/10.1007/BF03256650

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