The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1998/11/1739/ $5.00
The Journal of Experimental Medicine, Volume 188, Number 9, November 2, 1998 1739-1750


Articles

Essential Role of Nuclear Factor {kappa}B in the Induction of Eosinophilia in Allergic Airway Inflammation

Liyan Yang*, Lauren Cohn*,{ddagger}, Dong-Hong Zhang*, Robert Homer§, Anuradha Ray*, and Prabir Ray*

From the * Department of Internal Medicine, Pulmonary and Critical Care Section, the {ddagger} Section of Immunobiology, and the § Department of Pathology, Yale University School of Medicine, New Haven, Connecticut 06520

The molecular mechanisms that contribute to an eosinophil-rich airway inflammation in asthma are unclear. A predominantly T helper 2 (Th2)-type cell response has been documented in allergic asthma. Here we show that mice deficient in the p50 subunit of nuclear factor (NF)- {kappa}B are incapable of mounting eosinophilic airway inflammation compared with wild-type mice. This deficiency was not due to a block in T cell priming or proliferation in the p50–/– mice, nor was it due to a defect in the expression of the cell adhesion molecules VCAM-1 and ICAM-1 that are required for the extravasation of eosinophils into the airways. The major defects in the p50–/– mice were the lack of production of the Th2 cytokine interleukin 5 and the chemokine eotaxin, which are crucial for proliferation and for differentiation and recruitment, respectively, of eosinophils into the asthmatic airway. Additionally, the p50–/– mice were deficient in the production of the chemokines macrophage inflammatory protein (MIP)-1{alpha} and MIP-1β that have been implicated in T cell recruitment to sites of inflammation. These results demonstrate a crucial role for NF-{kappa}B in vivo in the expression of important molecules that have been implicated in the pathogenesis of asthma.

Key Words: allergic inflammation • eosinophils • nuclear factor {kappa}B • interleukin 5 • eotaxin


Address correspondence to Prabir Ray, Department of Internal Medicine, Pulmonary and Critical Care Section, Yale University School of Medicine, 333 Cedar St., LCI 105, New Haven, CT 06520. Phone: 203-785-3620; Fax: 203-785-3826; E-mail: prabir.ray{at}yale.edu

This paper is dedicated to the memory of our beloved mentor and friend Dr. Jyotirmoy Das of Indian Institute of Chemical Biology, India.

Abbreviations used: BAL, bronchoalveolar lavage; BALF, BAL fluid; EMSA, electrophoretic mobility shift assay; H&E, hematoxylin and eosin; ICAM, intercellular adhesion molecule; MCP, monocyte chemotactic protein; MIP, macrophage inflammatory protein; NF, nuclear factor; PLP, paraformaldehyde; RANTES, regulated on activation, normal T cell expressed and secreted; RT, reverse transcription; VCAM, vascular cell adhesion molecule.


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