Korean J Physiol Pharmacol.  2005 Dec;9(6):315-322.

Conditioned Medium from Dying Smooth Muscle Cell Induced Apoptotic Death

• Bu MH
• Lee KA
• Kim KH
• Rhim BY

Abstract

In this study, the authors investigated whether death of vascular smooth muscle cell (VSMC) had a pathological pertinence. Conditioned media obtained from rat aorta smooth muscle cell (SMC) that were induced death by expressing FADD in the absence of tetracycline (FADD-SMC) triggered death of normal SMC. DNA fragmentation and caspase-3 activation were observed in dying SMC by conditioned media. FADD-SMC showed transcriptional activation of tumor necrosis factor (TNF)-alpha. Conditioned medium contained TNF-alpha, indicating secretion of the cytokine from dying FADD-SMC. It was investigated if secreted TNF-alpha was functional. Conditioned medium activated ERK and p38 MAPK pathways and induced MMP-9 expression, whereas depletion of the cytokine with its soluble receptor (sTNFR) remarkably inhibited induction of MMP-9 by conditioned medium. These findings suggest that TNF-alpha in conditioned medium seems to be active. Then, contribution of TNF-alpha on death-inducing activity of conditioned medium was examined. Depletion of TNF-alpha with soluble TNF-alpha receptor decreased the death activity of conditioned medium by 35%, suggesting that TNF-alpha play a partial role in the death activity. Boiling of medium almost completely abolished the death-inducing activity, suggesting that other heat labile death inducing proteins existed in conditioned medium. Taken together, these results indicate that SMC undergoing death could contribute to inflammation by expressing inflammatory cytokines and pathological complications by inducing death of neighboring cells.

Keyword

Apoptosis; FADD; TNF-alpha; Vascular smooth muscle

MeSH Terms

Animals
Aorta
Apoptosis
Caspase 3
Culture Media, Conditioned*
Cytokines
DNA Fragmentation
Hot Temperature
Inflammation
Muscle, Smooth*
Muscle, Smooth, Vascular
Myocytes, Smooth Muscle*
p38 Mitogen-Activated Protein Kinases
Rats
Tetracycline
Transcriptional Activation
Tumor Necrosis Factor-alpha
Caspase 3
Culture Media, Conditioned
Cytokines
Tetracycline
Tumor Necrosis Factor-alpha
p38 Mitogen-Activated Protein Kinases