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Cited by 273

The DOI matches its Crossref record; 45 of the 45 references it cites were found in a registry or an index.

IL-8 Production in Human Lung Fibroblasts and Epithelial Cells Activated by the Pseudomonas Autoinducer N -3-Oxododecanoyl Homoserine Lactone Is Transcriptionally Regulated by NF-κB and Activator Protein-2

Open access
Smith, Roger S, Fedyk, Eric R, Springer, T A, Mukaida, N, Iglewski, Barbara H, Phipps, Richard P·2001·The Journal of Immunology
DOI 10.4049/jimmunol.167.1.366
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Abstract

The destructive pulmonary inflammation associated with Pseudomonas aeruginosa colonization is caused, in part, by the production of the chemokine IL-8, which recruits neutrophils into the lung. The Pseudomonas autoinducer, N-3-oxododecanoyl homoserine lactone (3-O-C12-HSL), is a small lipid-soluble molecule that is essential in the regulation of many P. aeruginosa virulence factors, but little is known about how it affects eukaryotic cells. In this report we demonstrate that 3-O-C12-HSL is a potent stimulator of both IL-8 mRNA and protein from human fibroblasts and epithelial cells in vitro. The IL-8 produced from these 3-O-C12-HSL-stimulated cells was found to be functionally active by inducing the chemotaxis of neutrophils. To determine a mechanism for this IL-8 induction, deletion constructs of the IL-8 promoter were examined. It was found that the DNA region between nucleotides −1481 and −546 and the transcription factor NF-κB were essential for the maximal induction of IL-8 by 3-O-C12-HSL. This was confirmed by EMSAs, where 3-O-C12-HSL induced a shift with both AP-2 and NF-κB consensus DNA. The activation of NF-κB and subsequent production of IL-8 were found to be regulated by a mitogen-activated protein kinase pathway. These findings support the concept that the severe lung damage that accompanies P. aeruginosa infections is caused by an exuberant neutrophil response stimulated by 3-O-C12-HSL-induced IL-8. Understanding the mechanisms of 3-O-C12-HSL activation of lung structural cells may provide a means to help control lung damage during infections with P. aeruginosa.

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Citations

Cites

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Metadata

Authors
Smith, R. S., Fedyk, E. R., Springer, T. A., Mukaida, N., Iglewski, B. H., & Phipps, R. P.
Venue
The Journal of Immunology
Publisher
Oxford University Press (OUP)
Published
2001-07-01
Volume
167
Issue
1
Pages
366-374
ISSN
  • 0022-1767 (ISSN-L)
  • 1550-6606
DOI
10.4049/jimmunol.167.1.366
OpenAlex
W1542204592
Cited by
273
References
45
FWCI
4.45
Type
journal article
Language
en
Open access
bronze

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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.

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