Eicosapentaenoic acid attenuates cigarette smoke-induced lung inflammation by inhibiting ROS-sensitive inflammatory signaling

Abstract

Cigarette smoking causes chronic lung inflammation that is mainly regulated by redox-sensitive pathways. Our previous studies have demonstrated that cigarette smoke (CS) activates reactive oxygen species (ROS)-sensitive mitogen-activated protein kinases (MAPKs)/nuclear factor-κB (NF-κB) signaling resulting in induction of lung inflammation. Eicosapentaenoic acid (EPA), a major type of omega-3 polyunsaturated fatty acid, is present in significant amounts in marine-based fish and fish oil. EPA has been shown to possess antioxidant and anti-inflammatory properties in vitro and in vivo. However, whether EPA has similar beneficial effects against CS-induced lung inflammation remains unclear. Using a murine model, we show that subchronic CS exposure for 4 weeks caused pulmonary inflammatory infiltration (total cell count in bronchoalveolar lavage fluid (BALF), 11.0-fold increase), increased lung vascular permeability (protein level in BALF, 3.1-fold increase), elevated levels of chemokines (11.4–38.2-fold increase) and malondialdehyde (an oxidative stress biomarker; 2.0-fold increase) in the lungs, as well as lung inflammation; all of these CS-induced events were suppressed by daily supplementation with EPA. Using human bronchial epithelial cells, we further show that CS extract (CSE) sequentially activated NADPH oxidase (NADPH oxidase activity, 1.9-fold increase), increased intracellular levels of ROS (3.0-fold increase), activated both MAPKs and NF-κB, and induced interleukin-8 (IL-8; 8.2-fold increase); all these CSE-induced events were inhibited by pretreatment with EPA. Our findings suggest a novel role for EPA in alleviating the oxidative stress and lung inflammation induced by subchronic CS exposure in vivo and in suppressing the CSE-induced IL-8 in vitro via its antioxidant function and by inhibiting MAPKs/NF-κB signaling.

Protective Action of Ostreococcus Tauri and Phaeodactylum Tricornutum Extracts towards Benzo[a]Pyrene-Induced Cytotoxicity in Endothelial Cells

“…It is interesting to note that many studies have linked the anti-inflammatory effects of compounds contained in microalgae with the inhibition of the NF-κB signaling pathway. A study on human bronchial epithelial cells also showed that EPA, by inhibiting MAPKs/NF-κB signaling, inhibits IL-8 induced by cigarette smoke extracts [85]. In another study, fucoxanthin was reported to reduce pro-inflammatory mediator levels via the inhibition of NF-κB pathway activation in murine macrophages [69].…”

Menthol Cigarette Smoke Induces More Severe Lung Inflammation Than Non-menthol Cigarette Smoke Does in Mice With Subchronic Exposure – Role of TRPM8

“…The lung inflammatory score was categorized according to the sum of the scores for the infiltration cell numbers and damage level, including the thickening of alveolar walls and epithelium. This grading method has been used in our previous studies (Liu et al, 2014; Lin et al, 2015).…”

“…In the present study, we hypothesized that M-CS could induce more severe lung inflammation than Non-M-CS could via the additional action of menthol on TRPM8. In testing this hypothesis, we employed a murine model of CS exposure (Tang et al, 2011; Liu et al, 2014; Wu et al, 2014) to compare various indices of lung inflammation and activation of MAPKs in lung tissues induced by subchronic exposure to Non-M-CS and M-CS. We used a selective TRPM8 antagonist ( N -(3-aminopropyl)-2-{[(3-methylphenyl) methyl]oxy}- N -(2-thienylmethyl) benzamide; AMTB) (Journigan and Zaveri, 2013) as the intervention to assess the role of TRPM8 in these responses.…”

Novel derivative of Paeonol, Paeononlsilatie sodium, alleviates behavioral damage and hippocampal dendritic injury in Alzheimer's disease concurrent with cofilin1/phosphorylated-cofilin1 and RAC1/CDC42 alterations in rats

“…Paeonol (2’-hydroxy-4’-methoxyacetophenone, C 9 H 10 O 3 ) is a phenolic acid compound extracted from the famous Cortex Moutan, which has been widely employed in traditional Chinese medicine (TCM). It is well established that Paeonol exerts anti-inflammatory activities to relieve ovalbumin-induced asthma [ 32 ] and cigarette smoke-induced lung inflammation [ 33 ] in a murine model, free-radical scavenging properties to prevent against neurotoxicity in vitro [ 34 , 35 ], and anti-tumor effects in culture cells [ 36 , 37 ]. Paeonol administration may reduce ischemia-reperfusion injured cerebral infarction [ 38 ] and ameliorate cognitive deficits in streptozotocin-induced diabetic rats [ 39 ].…”