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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 the increase in NADPH oxidase activity induced by cigarette smoke extract (CSE) in human bronchial epithelial cells. Cells were exposed to medium alone or to 3% CSE for 15 min with EPA (5 μM) or its vehicle. NADPH oxidase activity was measured by NADP+/NADPH assay. Data in each group are mean ± s.e.m. from five independent experiments. *p < 0.05 vs. control (vehicle without CSE stimulation). #p < 0.05 vs. CSE without EPA pretreatment.
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Figure 6: Eicosapentaenoic acid (EPA) attenuates the increase in NADPH oxidase activity induced by cigarette smoke extract (CSE) in human bronchial epithelial cells. Cells were exposed to medium alone or to 3% CSE for 15 min with EPA (5 μM) or its vehicle. NADPH oxidase activity was measured by NADP+/NADPH assay. Data in each group are mean ± s.e.m. from five independent experiments. *p < 0.05 vs. control (vehicle without CSE stimulation). #p < 0.05 vs. CSE without EPA pretreatment.

Mentions: Increases in intracellular ROS, via activation of NADHP oxidase, are an important trigger for the induction of IL-8 by CSE in HBECs (Tang et al., 2011; Wu et al., 2014). Compared to control cells, exposure of HBECs to 3% CSE for 30 min resulted in increases in intracellular levels of both superoxide (Figure 5A) and hydrogen peroxide (Figure 5B). The CSE-induced increases in intracellular ROS were prevented by pretreatment with EPA (Figure 5). Further analysis revealed that exposure of HBECs to 3% CSE for 15 min led to an increase in the activity of NADPH oxidase and this was found to be suppressed by pretreatment with EPA (Figure 6). Pretreatment with EPA in cells without CSE stimulation failed to alter the levels of intracellular ROS (Figure 5) and the activity of NADPH oxidase (Figure 6).


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 the increase in NADPH oxidase activity induced by cigarette smoke extract (CSE) in human bronchial epithelial cells. Cells were exposed to medium alone or to 3% CSE for 15 min with EPA (5 μM) or its vehicle. NADPH oxidase activity was measured by NADP+/NADPH assay. Data in each group are mean ± s.e.m. from five independent experiments. *p < 0.05 vs. control (vehicle without CSE stimulation). #p < 0.05 vs. CSE without EPA pretreatment.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 6: Eicosapentaenoic acid (EPA) attenuates the increase in NADPH oxidase activity induced by cigarette smoke extract (CSE) in human bronchial epithelial cells. Cells were exposed to medium alone or to 3% CSE for 15 min with EPA (5 μM) or its vehicle. NADPH oxidase activity was measured by NADP+/NADPH assay. Data in each group are mean ± s.e.m. from five independent experiments. *p < 0.05 vs. control (vehicle without CSE stimulation). #p < 0.05 vs. CSE without EPA pretreatment.
Mentions: Increases in intracellular ROS, via activation of NADHP oxidase, are an important trigger for the induction of IL-8 by CSE in HBECs (Tang et al., 2011; Wu et al., 2014). Compared to control cells, exposure of HBECs to 3% CSE for 30 min resulted in increases in intracellular levels of both superoxide (Figure 5A) and hydrogen peroxide (Figure 5B). The CSE-induced increases in intracellular ROS were prevented by pretreatment with EPA (Figure 5). Further analysis revealed that exposure of HBECs to 3% CSE for 15 min led to an increase in the activity of NADPH oxidase and this was found to be suppressed by pretreatment with EPA (Figure 6). Pretreatment with EPA in cells without CSE stimulation failed to alter the levels of intracellular ROS (Figure 5) and the activity of NADPH oxidase (Figure 6).

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