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Stretch-induced IL-6 secretion from endothelial cells requires NF-kappaB activation
Satoshi Kobayashi1, Masato Nagino, Shunichiro Komatsu
1Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
Biochemical and Biophysical Research Communications
|August 7, 2003
Summary
Mechanical stress on endothelial cells (ECs) triggers interleukin-6 (IL-6) secretion via sequential activation of IkappaB kinase (IKK) and NF-kappaB pathways. This mechanism is crucial for cellular responses to stretch.
Area of Science:
- Cell Biology
- Molecular Biology
- Physiology
Background:
- Endothelial cells (ECs) mediate regenerative and inflammatory responses.
- Mechanical stimuli influence EC functions, including cytokine secretion.
- Interleukin-6 (IL-6) is a key mediator in these processes.
Purpose of the Study:
- To elucidate the mechanism of IL-6 secretion from ECs under uni-axial continuous stretch.
- To identify the signaling pathways involved in stretch-induced IL-6 release.
Main Methods:
- Human umbilical vein endothelial cells (HUVECs) were subjected to uni-axial continuous stretch.
- IL-6 secretion levels were measured.
- Gene transcription (RT-PCR) and IkappaB kinase (IKK) activity were assessed.
- NF-kappaB pathway activation was inhibited using chemical inhibitors and antisense oligodeoxynucleotides.
Main Results:
- Continuous stretch induced a dose-dependent increase in IL-6 secretion from HUVECs.
- IL-6 gene transcription peaked at 2 hours post-stretch.
- IKK activation peaked at 15 minutes post-stretch.
- Inhibition of IKK and NF-kappaB significantly suppressed stretch-induced IL-6 mRNA expression.
Conclusions:
- Uni-axial continuous stretch activates the IKK/NF-kappaB signaling pathway in ECs.
- This pathway sequentially leads to increased IL-6 gene expression and secretion.
- Understanding this mechanism is vital for studying ECs' role in mechanical stress responses.