Abstract
Interleukin (IL)-1 modulates the expression of various genes in normal and tumor cells. We investigated the molecular mechanisms underlying IL-1β-induced expression of IL-8 mRNA and protein in human vascular smooth muscle cells (hVSMCs). P38 mitogen-activated protein kinase (MAPK) was activated after 5 min of IL-1β treatment, whereas the extracellular signal-regulated kinases, the c-jun amino-terminal kinases, and protein kinase B/Akt were not activated by IL-1β. IL-1β induced activation of a full-length IL-8 promoter-reporter construct. Deletional mutagenesis localized the IL-1β-responsive domains to two regions (- 133 to - 98 and - 85 to - 50) that contain consensus binding sites for activator protein-1 (AP-1) and nuclear factor-κB (NF-κB), respectively. Site-directed mutagenesis of the 133-bp minimal promoter confirmed that these sites were required for promoter activity. Electrophoretic mobility shift assays confirmed that IL-1β increased AP-1 and NF-κB DNA-binding activities in a time-dependent manner. SB203580, a specific P38 MAPK inhibitor, partially blocked IL-1β induction of IL-8 mRNA, IL-8 promoter activity, and AP-1 nuclear extract binding but not NF-κB DNA binding. Our data demonstrate that AP-1 and NF-κB are essential transcription factors for IL-1β-induced IL-8 gene expression in hVSMCs. P38 MAPK is involved in inducing IL-8 gene transcription via AP-1 activation in hVSMCs.
Original language | English (US) |
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Pages (from-to) | 206-213 |
Number of pages | 8 |
Journal | Cytokine |
Volume | 18 |
Issue number | 4 |
DOIs | |
State | Published - May 2002 |
Externally published | Yes |
Keywords
- AP-1
- Interleukin-1 beta
- Interleukin-8
- Mitogen-activated protein kinase
- NF-kappa B
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
- Biochemistry
- Hematology
- Molecular Biology