Stretch-induced IL-6 secretion from endothelial cells requires NF-kappaB activation.
Interleukin-6 (IL-6) secretion from endothelial cells (ECs) in response to mechanical stimuli plays an important role in the regenerative and inflammatory responses. The aim of this study was to determine the mechanism for the secretion of IL-6 from ECs in response to uni-axial continuous stretch. Continuous stretch induced IL-6 secretion from human umbilical vein endothelial cells (HUVECs) in a dose-dependent manner. Reverse transcriptase-polymerase chain reaction (RT-PCR) amplification showed that the transcription of the IL-6 gene peaked 2h after stretch. In vitro kinase assay of IkappaB kinase (IKKs) activity demonstrated that the activation of IKKs peaked 15 min after stretch. Two NF-kappaB inhibitors, pyrrolidine dithiocarbamanate (PDTC) and SN50, or antisense oligodeoxynucleotides for NF-kappaB p65 and p50 suppressed IL-6 mRNA expressions induced by continuous stretch. In conclusion, continuous stretch induces IL-6 secretion from ECs, most likely through sequential activation of IKKs and NF-kappaB.
Kobayashi
Satoshi
S
Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
Nagino
Masato
M
Komatsu
Shunichiro
S
Naruse
Keiji
K
Nimura
Yuji
Y
Nakanishi
Makoto
M
Sokabe
Masahiro
M
D001483:Base Sequence; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000276:immunology* / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D051550:I-kappa B Kinase; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D052002:NF-kappa B p50 Subunit; D020319:Oligodeoxyribonucleotides, Antisense / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013314:Stress, Mechanical; D051996:Transcription Factor RelA
D015850:Interleukin-6; D016328:NF-kappa B; D052002:NF-kappa B p50 Subunit; D020319:Oligodeoxyribonucleotides, Antisense; D012333:RNA, Messenger; D051996:Transcription Factor RelA; D017346:Protein Serine-Threonine Kinases; C496559:CHUK protein, human; D051550:I-kappa B Kinase; C496560:IKBKB protein, human; C496565:IKBKE protein, human