Exacerbation of tumor necrosis factor-induced vascular leak syndrome by aging.
Aging is associated with upregulation of tumor necrosis factor (TNF) and increased vascular inflammation. TNF is a major proinflammatory cytokine that contributes to both vascular inflammation and vascular leak syndrome (VLS). The purpose of this study was to investigate whether the aging affects TNF-induced VLS. Vascular leak, histology, and cytokine assays were performed in young and aged groups of wild-type and TNF overexpressing transgenic (Tg) mice. An aged group of TNF Tg mice showed substantially amplified VLS compared with young Tg mice. Age-related amplification of TNF-induced VLS appears to be related to local vascular fibrosis and the systemic upregulation of TNF and MCP-1 levels in older TNF Tg mice. Our finding suggests that chronic high-grade TNF exposure could mediate the severe vascular pathogenicity of VLS.
Integrated Research Institute of Pharmaceutical Sciences, College of Pharmacy, The Catholic University of Korea, Bucheon, Republic of Korea.
Kyung-Yeon
KY
Park
Department of Biotechnology, Hoseo University, Baebang, Asan, Chungnam, Republic of Korea.
Sung-Jo
SJ
Kim
Integrated Research Institute of Pharmaceutical Sciences, College of Pharmacy, The Catholic University of Korea, Bucheon, Republic of Korea.
Euichaul
E
Oh
Integrated Research Institute of Pharmaceutical Sciences, College of Pharmacy, The Catholic University of Korea, Bucheon, Republic of Korea. Electronic address: thhur92@catholic.ac.kr.
Tae-Hwe
TH
Heo
D000375:Aging / Q000502:physiology*; D000818:Animals; D019559:Capillary Leak Syndrome / Q000473:pathology*; D018932:Chemokine CCL2 / Q000235:genetics; D007249:Inflammation / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation / Q000502:physiology
C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D014409:Tumor Necrosis Factor-alpha
Aging; TNF; VLS; Vascular leak syndrome