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

Liu MH, Lin AH, Lu SH, Peng RY, Lee TS, Kou YR - Front Physiol (2014)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, School of Medicine, National Yang-Ming University Taipei, Taiwan.

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.

No MeSH data available.


Related in: MedlinePlus

Eicosapentaenoic acid (EPA) attenuates cigarette smoke (CS)-induced increases in total protein content (A), total cell count (B) and differential cell count (C) in bronchoalveolar lavage fluid (BALF). These indices were measured and served as indications of lung inflammation. Data in each group are mean ± s.e.m. from 6 mice. *p < 0.05 vs. the air-exposure group; #p < 0.05 vs. the CS-exposure group with vehicle treatment. See the legend of Figure 1 for detailed information on each study group.
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Figure 2: Eicosapentaenoic acid (EPA) attenuates cigarette smoke (CS)-induced increases in total protein content (A), total cell count (B) and differential cell count (C) in bronchoalveolar lavage fluid (BALF). These indices were measured and served as indications of lung inflammation. Data in each group are mean ± s.e.m. from 6 mice. *p < 0.05 vs. the air-exposure group; #p < 0.05 vs. the CS-exposure group with vehicle treatment. See the legend of Figure 1 for detailed information on each study group.

Mentions: Exposure of mice to CS for 4 weeks resulted in the development of lung inflammation as evidenced by the histological evaluation of the H&E stained lung sections. The inflammatory manifestations included extensive infiltration of inflammatory cells, thickening of the alveolar walls and the presence of abnormal re-epithelialization in the CS-exposure mice (Figures 1A,B); these changes were found to be less in the CS-exposure mice that underwent EPA treatment (Figures 1A,B). Comparisons of the group data in terms of lung inflammatory scores confirmed this difference in the degree of histopathological manifestations between the CS-exposure mice with and without EPA treatment (Figure 1C). Additionally, compared to the air-exposure mice, the CS-exposure mice were found to show increases in total protein levels (Figure 2A), total cell counts (Figure 2B) and differential cell counts (Figure 2C) in BALF. All of these inflammatory indices were significantly alleviated in the CS-exposure mice that underwent EPA treatment (Figure 2). These inflammatory manifestations were not found in the air-exposure mice that underwent EPA treatment (Figures 1, 2).


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

Liu MH, Lin AH, Lu SH, Peng RY, Lee TS, Kou YR - Front Physiol (2014)

Eicosapentaenoic acid (EPA) attenuates cigarette smoke (CS)-induced increases in total protein content (A), total cell count (B) and differential cell count (C) in bronchoalveolar lavage fluid (BALF). These indices were measured and served as indications of lung inflammation. Data in each group are mean ± s.e.m. from 6 mice. *p < 0.05 vs. the air-exposure group; #p < 0.05 vs. the CS-exposure group with vehicle treatment. See the legend of Figure 1 for detailed information on each study group.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4231989&req=5

Figure 2: Eicosapentaenoic acid (EPA) attenuates cigarette smoke (CS)-induced increases in total protein content (A), total cell count (B) and differential cell count (C) in bronchoalveolar lavage fluid (BALF). These indices were measured and served as indications of lung inflammation. Data in each group are mean ± s.e.m. from 6 mice. *p < 0.05 vs. the air-exposure group; #p < 0.05 vs. the CS-exposure group with vehicle treatment. See the legend of Figure 1 for detailed information on each study group.
Mentions: Exposure of mice to CS for 4 weeks resulted in the development of lung inflammation as evidenced by the histological evaluation of the H&E stained lung sections. The inflammatory manifestations included extensive infiltration of inflammatory cells, thickening of the alveolar walls and the presence of abnormal re-epithelialization in the CS-exposure mice (Figures 1A,B); these changes were found to be less in the CS-exposure mice that underwent EPA treatment (Figures 1A,B). Comparisons of the group data in terms of lung inflammatory scores confirmed this difference in the degree of histopathological manifestations between the CS-exposure mice with and without EPA treatment (Figure 1C). Additionally, compared to the air-exposure mice, the CS-exposure mice were found to show increases in total protein levels (Figure 2A), total cell counts (Figure 2B) and differential cell counts (Figure 2C) in BALF. All of these inflammatory indices were significantly alleviated in the CS-exposure mice that underwent EPA treatment (Figure 2). These inflammatory manifestations were not found in the air-exposure mice that underwent EPA treatment (Figures 1, 2).

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, School of Medicine, National Yang-Ming University Taipei, Taiwan.

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.

No MeSH data available.


Related in: MedlinePlus