https://scholars.lib.ntu.edu.tw/handle/123456789/594002
標題: | Carbon Monoxide-Releasing Molecule-2 Ameliorates Particulate Matter-Induced Aorta Inflammation via Toll-Like Receptor/NADPH Oxidase/ROS/NF-κB/IL-6 Inhibition | 作者: | Vo, Thi Thuy Tien Hsu, Chien-Yi Wee, Yinshen YUH-LIEN CHEN Cheng, Hsin-Chung Wu, Ching-Zong Lin, Wei-Ning Lee, I-Ta |
關鍵字: | NF-KAPPA-B; SMOOTH-MUSCLE-CELLS; NADPH OXIDASE; EXTRAPULMONARY TRANSLOCATION; NAD(P)H OXIDASE; EXPRESSION; INTERLEUKIN-6; MIGRATION; PARTICLES; FINE | 公開日期: | 2021 | 出版社: | HINDAWI LTD | 卷: | 2021 | 來源出版物: | Oxidative medicine and cellular longevity | 摘要: | Particulate matter (PM), a major air pollutant, may be associated with adverse cardiovascular effects. Reactive oxygen species- (ROS-) dependent proinflammatory cytokine production, such as interleukin-6 (IL-6), is a possible underlying mechanism. Carbon monoxide- (CO-) releasing molecule-2 (CORM-2) which liberates exogenous CO can exert many beneficial effects, particularly anti-inflammation and antioxidant effects. The purpose of this study was to explore the protective effects and underpinning mechanisms of CORM-2 on PM-induced aorta inflammation. Here, human aortic vascular smooth muscle cells (HASMCs) were utilized as in vitro models for the assessment of signaling pathways behind CORM-2 activities against PM-induced inflammatory responses, including Toll-like receptors (TLRs), NADPH oxidase, ROS, nuclear factor-kappa B (NF-κB), and IL-6. The modulation of monocyte adherence and HASMC migration, that are two critical cellular events of inflammatory process, along with their regulators, including intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and matrix metalloproteinase-2 (MMP-2) and MMP-9, in response to PM by CORM-2, were further evaluated. Finally, mice experiments under different conditions were conducted for the in vivo evaluation of CORM-2 benefits on the expression of inflammatory molecules including IL-6, ICAM-1, VCAM-1, MMP-2, and MMP-9. Our results found that PM could induce aorta inflammation in vitro and in vivo, as evidenced by the increase of IL-6 expression that was regulated by the TLR2 and TLR4/NADPH oxidase/ROS/NF-κB signaling pathway, thereby promoting ICAM-1- and VCAM-1-dependent monocyte adhesion and MMP-2- and MMP-9-dependent HASMC migration. Importantly, our experimental models demonstrated that CORM-2-liberated CO effectively inhibited the whole identified PM-induced inflammatory cascade in HASMCs and tissues. In conclusion, CORM-2 treatment may elicit multiple beneficial effects on inflammatory responses of aorta due to PM exposure, thereby providing therapeutic value in the context of inflammatory diseases of the cardiovascular system. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/594002 | ISSN: | 1942-0900 | DOI: | 10.1155/2021/2855042 | SDG/關鍵字: | Blood vessels; Carbon monoxide; Cell adhesion; Cell signaling; Diseases; Mammals; Muscle; Particles (particulate matter); Pathology; Inflammatory disease; Inflammatory response; Intercellular adhesion molecule-1; Matrix metalloproteinase-2; Nuclear factor kappaB; Proinflammatory cytokines; Vascular cell adhesion molecule-1; Vascular Smooth Muscle Cells; Molecules; acetylcysteine; apocynin; carbon monoxide; diphenyliodonium salt; gelatinase A; gelatinase B; helenalin; immunoglobulin enhancer binding protein; intercellular adhesion molecule 1; interleukin 6; messenger RNA; reactive oxygen metabolite; reduced nicotinamide adenine dinucleotide phosphate oxidase; toll like receptor; toll like receptor 2; toll like receptor 4; tricarbonyldichlororuthenium ii dimer; unclassified drug; vascular cell adhesion molecule 1; interleukin 6; organometallic compound; reactive oxygen metabolite; reduced nicotinamide adenine dinucleotide phosphate oxidase; tricarbonyldichlororuthenium (II) dimer; animal experiment; animal model; aorta; Article; cell adhesion; cell migration; cell viability; controlled study; human; human cell; in vitro study; inflammation; male; monocyte; mouse; nonhuman; particulate matter; protein expression; signal transduction; vascular smooth muscle cell; animal; aorta; drug effect; inflammation; metabolism; pathology; Adhesion; Cad Cam; Carbon Monoxide; Cells; Migration; Models; Processes; Release; Animals; Aorta; Humans; Inflammation; Interleukin-6; Male; Mice; NADPH Oxidases; Organometallic Compounds; Reactive Oxygen Species |
顯示於: | 解剖學暨細胞生物學科所 |
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