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Multiple control of interleukin‐8 gene expression
Author(s) -
Hoffmann Elke,
DittrichBreiholz Oliver,
Holtmann Helmut,
Kracht Michael
Publication year - 2002
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.72.5.847
Subject(s) - biology , proinflammatory cytokine , derepression , chemokine , transcription factor , gene expression , microbiology and biotechnology , signal transduction , kinase , tumor necrosis factor alpha , regulation of gene expression , p38 mitogen activated protein kinases , gene , interleukin 8 , interleukin , protein kinase a , cytokine , inflammation , immunology , genetics , psychological repression
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.