Uni-axial cyclic stretch induces the activation of transcription factor nuclear factor kappaB in human fibroblast cells.
The effect of uni-axial cyclic mechanical stretch on the activation of the transcription factor nuclear factor kappaB (NF-kappaB) was investigated in a human fibroblast cell line (TIG-1). In response to uni-axial cyclic stretch, NF-kappaB was found to be translocated into the nucleus. The NF-kappaB was first detectable 2 min after the onset of stretch and then peaked at 4 min and returned to the basal level within 10 min. To investigate whether NF-kappaB is activated following the translocation into the nucleus, we measured the luciferase activity in the cells transfected with pNF-kappaB-luciferase. The activity of luciferase increased 4 min after the initiation of cyclic stretch, peaked at 15 min (6.4-fold increase), and decreased gradually. We examined the involvement of the stretch-activated (SA) channel in the stretch-induced NF-kappaB activation. The application of Gd3+, a blocker of the SA channel, or the removal of extracellular Ca2+ inhibited both the translocation into the nucleus and the activation of NF-kB, which suggests that NF-kappaB is activated by uni-axial cyclic stretch via SA channel activation in human lung fibroblasts.
Inoh
Hidefumi
H
Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine, Cell Mechano-sensing Project, ICORP, JST, Nagoya 466-8550, Japan.
Ishiguro
Naoki
N
Sawazaki
Shin-Ichi
S
Amma
Hideki
H
Miyazu
Motoi
M
Iwata
Hisashi
H
Sokabe
Masahiro
M
Naruse
Keiji
K
D021581:Active Transport, Cell Nucleus; D015220:Calcium Channels / Q000502:physiology; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D051546:Cyclooxygenase 2; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics; D007700:Kinetics; D008565:Membrane Proteins; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism*; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D013314:Stress, Mechanical
D015220:Calcium Channels; D007527:Isoenzymes; D008565:Membrane Proteins; D016328:NF-kappa B; D012333:RNA, Messenger; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases