Carbon Monoxide-Releasing Molecule-2 Ameliorates Particulate Matter-Induced Aorta Inflammation via Toll-Like Receptor/NADPH Oxidase/ROS/NF-κB/IL-6 Inhibition.
Thi Thuy Tien VoChien-Yi HsuYinshen WeeYuh-Lien ChenHsin-Chung ChengChing-Zong WuWei-Ning LinI-Ta LeePublished in: Oxidative medicine and cellular longevity (2021)
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.
Keyphrases
- particulate matter
- nuclear factor
- toll like receptor
- oxidative stress
- air pollution
- diabetic rats
- signaling pathway
- cell adhesion
- reactive oxygen species
- dna damage
- high glucose
- aortic valve
- cell migration
- endothelial cells
- pulmonary artery
- inflammatory response
- pi k akt
- vascular smooth muscle cells
- cell death
- poor prognosis
- induced apoptosis
- immune response
- polycyclic aromatic hydrocarbons
- drug induced
- dendritic cells
- lps induced
- gene expression
- mouse model
- heavy metals
- emergency department
- pulmonary hypertension
- adipose tissue
- water soluble
- heart failure
- epithelial mesenchymal transition
- escherichia coli
- left ventricular
- cell proliferation
- metabolic syndrome
- insulin resistance
- biofilm formation
- transcription factor
- aortic dissection
- long non coding rna