Cited by 1,058Chemokine receptors and signalingNF-κB Signaling PathwaysCytokine Signaling Pathways and Interactions

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Multiple control of interleukin-8 gene expression

Hoffmann, Elke, Dittrich-Breiholz, Oliver, Holtmann, Helmut, Kracht, Michael·2002·Journal of Leukocyte Biology

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Abstract

Interleukin (IL)-8, a prototypic human chemokine, was detected more than a decade ago as the founding member of the chemokine superfamily. One of the most remarkable properties of IL-8 is the variation of its expression levels. In healthy tissues, IL-8 is barely detectable, but it is rapidly induced by ten- to 100-fold in response to proinflammatory cytokines such as tumor necrosis factor or IL-1, bacterial or viral products, and cellular stress. Recently, significant advances in the understanding of signaling pathways, which coordinately regulate IL-8 transcription as well as mRNA stabilization in response to external stimuli, have been made. Maximal IL-8 amounts are generated by a combination of three different mechanisms: first, derepression of the gene promoter; second, transcriptional activation of the gene by nuclear factor-κB and JUN-N-terminal protein kinase pathways; and third, stabilization of the mRNA by the p38 mitogen-activated protein kinase pathway. In that way, cells are able to rapidly increase and at the same time, to fine-tune the amount of IL-8 secreted and thereby control the extent of leukocytes attracted to sites of tissue injury.

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Authors: Hoffmann, E., Dittrich-Breiholz, O., Holtmann, H., & Kracht, M.
Affiliations: Medizinische Hochschule Hannover (DE)
Institute of Pharmacology, Medical School Hannover , Germany
Corresponding author: Kracht, Michael
ORCID: Hoffmann, Elke
Kracht, Michael
Venue: Journal of Leukocyte Biology
Publisher: Oxford University Press (OUP)
Published: 2002-11-01
Volume: 72
Issue: 5
Pages: 847-855
ISSN: 0741-5400 (ISSN-L)
1938-3673
DOI: 10.1189/jlb.72.5.847
OpenAlex: W2149122802
Cited by: 1,058
References: 87
Citations by year: 2026: 15 · 2025: 20 · 2024: 17 · 2023: 35 · 2022: 37 · 2021: 35 · 2020: 31 · 2019: 35 · 2018: 37 · 2017: 39 · 2016: 49 · 2015: 79 · 2014: 64 · 2013: 54 · 2012: 39
FWCI: 17.59
Type: journal article
Language: en
Open access: closed
Licence: academic.oup.com/pages/standard-publication-reuse-rights (vor)
Locations: Journal of Leukocyte Biology (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Oncology › Chemokine receptors and signaling
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
Life Sciences › Immunology and Microbiology › Immunology › Cytokine Signaling Pathways and Interactions
Keywords: interleukin-8, chemokines, gene expression regulation, transcriptional activation, NF-κB, JNK signaling, p38 MAPK, mRNA stabilization, inflammatory cytokines, chemokine induction, leukocyte recruitment
MeSH terms: Animals, Base Sequence, DNA-Binding Proteins, Gene Expression Regulation, Humans, Molecular Sequence Data, Repressor Proteins, Transcription Factors, Transcription, Genetic, Signal Transduction, Transcriptional Activation, Interleukin-8, NF-kappa B, RNA Stability, Mitogen-Activated Protein Kinases, MAP Kinase Kinase Kinases, Mice

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