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 2 It 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. (C) 2003 Elsevier Inc. All rights reserved.