| Autor: |
Kuwahara, Ippei, Lillehoj, Erik P., Wenju Lu, Singh, Ishwar S., Isohama, Yoichiro, Miyata, Takeshi, Kim, K. Chul |
| Předmět: |
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| Zdroj: |
American Journal of Physiology: Lung Cellular & Molecular Physiology; Sep2006, Vol. 291, pL407-L416, 10p, 11 Graphs |
| Abstrakt: |
In this study, we investigated the regulation and mechanism of IL-8 expression by A549 human lung carcinoma cells treated with neutrophil elastase (NE). NE-treated cells exhibited significantly higher IL-8 protein levels in culture media compared with cells treated with vehicle alone. Blocking of gene transcription with actinomycin D suggested that NE stimulated IL-8 synthesis via increased mRNA expression, which was verified by real-time RT-PCR. NE activated the IL-8 promoter but did not alter the stability of its mRNA, confirming that the protease induced IL-8 synthesis through increased gene transcription. The results from the use of chemical inhibitors and mutant gene constructs against various signal transduction components seem to suggest the linear signaling pathway involving the activation of PKC-δ→ dual oxidase 1 → reactive oxygen species TNF-α-converting enzyme → EGF receptor → p38 → NF-κB for NE-activated IL-8 gene expression. A NF-κB potential binding site, located between nucleotides -82 and -69 of the IL-8 promoter, was identified as necessary for NE-induced IL-8 transcription. We conclude that NE increases IL-8 transcription through p38/NF-κB activation via EGFR transactivation. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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