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Published ahead of print on April 24, 2003, doi:10.1165/rcmb.2002-0306OC
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American Journal of Respiratory Cell and Molecular Biology. Vol. 29, pp. 483-489, 2003
© 2003 American Thoracic Society
DOI: 10.1165/rcmb.2002-0306OC

Serum and Low-Density Lipoprotein Enhance Interleukin-8 Secretion by Airway Epithelial Cells

James E. Gern, Rebecca Brockman-Schneider, Saswati Bhattacharya, James S. Malter and William W. Busse

Departments of Pediatrics, Pathology, and Medicine, University of Wisconsin-Madison, Madison, Wisconsin

Address correspondence to: James E. Gern, M.D., K4/918 CSC, 600 Highland Avenue, Madison, WI 53792-9988. E-mail: gern{at}medicine.wisc.edu

Viral respiratory infections rapidly increase vascular permeability, which leads to the transudation of serum proteins into airway secretions and tissues. To determine whether this process activates airway epithelial cells, bronchial epithelial cells were incubated with serum, and interleukin (IL)-8 secretion and gene expression were examined. As little as 0.1% serum significantly enhanced IL-8 secretion, and maximal secretion (65 ± 4 ng/ml, 48 h) was observed with 10% serum. Low-density lipoprotein, but not albumin or immunoglobulin G, augmented bronchial epithelial IL-8 secretion, which was partially blocked by a monoclonal antibody specific for the low-density lipoprotein receptor. The IL-8–inducing activity of plasma was also augmented by clotting and platelet activation. Mechanistically, serum activated nuclear factor-{kappa}B and increased the stability and steady state levels of IL-8 mRNA. In summary, specific components of serum are potent activators of IL-8 mRNA and secretion, and the increased IL-8 production is likely to be a result of both increased transcription and mRNA stability. This effect may represent an innate mechanism for the recruitment of neutrophils to the airway in response to noxious stimuli, such as viral infections, that increase vascular permeability.

Abbreviations: bronchial epithelial, BE • bronchial epithelial growth medium, BEGM • granulocyte-colony stimulating factor, G-CSF • immunoglobulin, Ig • interleukin, IL • low-density lipoprotein, LDL • nuclear factor-{kappa}B, NF-{kappa}B • rhinovirus, RV • tumor necrosis factor-{alpha}, TNF-{alpha}




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