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.