Conditioned Medium from Dying Smooth Muscle Cell Induced Apoptotic Death

• 영문명: Conditioned Medium from Dying Smooth Muscle Cell Induced Apoptotic Death
• 발행기관: 대한생리학회-대한약리학회
• 저자명: Moon Hyun Bu Kyeong Ah Lee Koan Hoi Kim Byung Yong Rhim
• 간행물 정보: 『The Korean Journal of Physiology & Pharmacology』제9권 제6호, 315~322쪽, 전체 8쪽
• 주제분류: 의약학 > 의학일반
• 파일형태: PDF
• 발행일자: 2005.01.01

영문 초록

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)-α. Conditioned medium contained TNF-α, indicating secretion of the cytokine from dying FADD-SMC. It was investigated if secreted TNF-α 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-α in conditioned medium seems to be active. Then, contribution of TNF-α on death-inducing activity of conditioned medium was examined. Depletion of TNF-α with soluble TNF-α receptor decreased the death activity of conditioned medium by 35%, suggesting that TNF-α 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.

키워드

Apoptosis FADD TNF-α Vascular smooth muscle