Lycopene Inhibits Oxidative Stress-Mediated Inflammatory Responses in Ethanol/Palmitoleic Acid-Stimulated Pancreatic Acinar AR42J Cells

Lee, Jae-Eun; Lim, Joo Weon; Kim, Hye Young

doi:10.3390/ijms22042101

Cited by 29 publications

(26 citation statements)

References 44 publications

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“…These results indicate that Ca 2+ is upstream activator for NADPH oxidase in pancreatic acinar cells stimulated with cerulean/resistin. We previously showed that lycopene inhibits oxidative stressmediated expression of IL-6 by suppressing the NADPH oxidase activity in ethanol/palmitoleic acid-stimulated pancreatic acinar AR42J cells [52]. Our previous and present findings suggest the involvement of NADPH oxidase on the pathogenesis of acute pancreatitis.…”

Section: Mediators Of Inflammationsupporting

confidence: 70%

Astaxanthin Inhibits Interleukin-6 Expression in Cerulein/Resistin-Stimulated Pancreatic Acinar Cells

Kwak

Lim

Kim

2021

Mediators of Inflammation

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Acute pancreatitis is a common clinical condition with increasing the proinflammatory mediators, including interleukin-6 (IL-6). Obesity is a negative prognostic factor in acute pancreatitis. Obese patients with acute pancreatitis have a higher systemic inflammatory response rate. Levels of serum resistin, an adipocytokine secreted by fat tissues, increase with obesity. Cerulein, a cholecystokinin analog, induces calcium (Ca2+) overload, oxidative stress, and IL-6 expression in pancreatic acinar cells, which are hallmarks of acute pancreatitis. A recent study showed that resistin aggravates the expression of inflammatory cytokines in cerulein-stimulated pancreatic acinar cells. We aimed to investigate whether resistin amplifies cerulein-induced IL-6 expression and whether astaxanthin (ASX), an antioxidant carotenoid with anti-inflammatory properties, inhibits ceruelin/resistin-induced IL-6 expression in pancreatic acinar AR42J cells. We found that resistin enhanced intracellular Ca2+ levels, NADPH oxidase activity, intracellular reactive oxygen species (ROS) production, NF-κB activity, and IL-6 expression in cerulein-stimulated AR42J cells, which were inhibited by ASX in a dose-dependent manner. The calcium chelator BAPTA-AM inhibited cerulein/resistin-induced NADPH oxidase activation and ROS production. Antioxidant N-acetyl cysteine (NAC) and ML171, a specific NADPH oxidase 1 inhibitor, suppressed cerulein/resistin-induced ROS production, NF-κB activation, and IL-6 expression. In conclusion, ASX inhibits IL-6 expression, by reducing Ca2+ overload, NADPH oxidase-mediated ROS production, and NF-κB activity in cerulein/resistin-stimulated pancreatic acinar cells. Consumption of ASX-rich foods could be beneficial for preventing or delaying the incidence of obesity-associated acute pancreatitis.

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Section: Mediators Of Inflammationsupporting

confidence: 70%

Astaxanthin Inhibits Interleukin-6 Expression in Cerulein/Resistin-Stimulated Pancreatic Acinar Cells

Kwak

Lim

Kim

2021

Mediators of Inflammation

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“…Based on the previous studies [6,56] showing that HDM enter the airway epithelium and induce mitochondrial fission, it is necessary to determine whether HDM induce mitochondrial dysfunction by directly interacting with mitochondria for further study. Since HDM stimulate NADPH oxidase in airway epithelial cells [10] and lycopene inhibits NADPH oxidase in various cells [32][33][34], it should be performed to determine whether lycopene inhibits NADPH oxidase in HDM-stimulated cells. Based on the previous studies [6,56] showing that HDM enter the airway epithelium and induce mitochondrial fission, it is necessary to determine whether HDM induce mitochondrial dysfunction by directly interacting with mitochondria for further study.…”

Section: Discussionmentioning

confidence: 99%

“…Thus, reducing ROS through lycopene may suppress TLR 4 recruitment into lipid rafts and inhibit the activation of downstream signaling pathways, such as MAPKs and NF-κB. Previously, we and others showed that lycopene inhibits NADPH oxidase activity in various cells [ 32 , 33 , 34 ]. Therefore, lycopene may inhibit NADPH oxidase in HDM-stimulated cells.…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

“…Zou et al [ 31 ] showed that lycopene suppresses IL-6 expression in LPS-stimulated macrophages by inhibiting the ROS-induced trafficking of TLR4 to lipid raft-like domains. Recently, we showed that lycopene inhibits NADPH oxidase activity and thus reduces ROS levels, leading to inhibition of NF-kB activation, IL-6 expression in pancreatic acinar cells stimulated with ethanol and palmitoleic acid [ 32 ]. Jhou et al [ 33 ] demonstrated that lycopene downregulates NADPH oxidase 4 protein expression of human liver adenocarcinoma SKHep-1 cells.…”

Section: Introductionmentioning

confidence: 99%

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Lycopene Inhibits Toll-Like Receptor 4-Mediated Expression of Inflammatory Cytokines in House Dust Mite-Stimulated Respiratory Epithelial Cells

2021

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House dust mites (HDM) are critical factors in airway inflammation. They activate respiratory epithelial cells to produce reactive oxygen species (ROS) and activate Toll-like receptor 4 (TLR4). ROS induce the expression of inflammatory cytokines in respiratory epithelial cells. Lycopene is a potent antioxidant nutrient with anti-inflammatory activity. The present study aimed to investigate whether HDM induce intracellular and mitochondrial ROS production, TLR4 activation, and pro-inflammatory cytokine expression (IL-6 and IL-8) in respiratory epithelial A549 cells. Additionally, we examined whether lycopene inhibits HDM-induced alterations in A549 cells. The treatment of A549 cells with HDM activated TLR4, induced the expression of IL-6 and IL-8, and increased intracellular and mitochondrial ROS levels. TAK242, a TLR4 inhibitor, suppressed both HDM-induced ROS production and cytokine expression. Furthermore, lycopene inhibited the HDM-induced TLR4 activation and cytokine expression, along with reducing the intracellular and mitochondrial ROS levels in HDM-treated cells. These results collectively indicated that the HDM induced TLR4 activation and increased intracellular and mitochondrial ROS levels, thus resulting in the induction of cytokine expression in respiratory epithelial cells. The antioxidant lycopene could inhibit HDM-induced cytokine expression, possibly by suppressing TLR4 activation and reducing the intracellular and mitochondrial ROS levels in respiratory epithelial cells.

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Lycopene Regulates Dietary Dityrosine‐Induced Mitochondrial‐Lipid Homeostasis by Increasing Mitochondrial Complex Activity

Wang

Tang

et al. 2021

Molecular Nutrition Food Res

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Scope: Dityrosine (DT), a marker of protein oxidation, is widely found in many high-protein foods. Dietary intake of DT induces myocardial oxidative stress injury and impairs energy metabolism. Lycopene is a common dietary supplement with antioxidant and mitochondrial-lipid homeostasis modulating abilities. This study aimed to examine the effects of lycopene on DT-induced disturbances in myocardial function and energy metabolism. Methods and Results: Four-week-old C57BL/6J mice received intragastric administration of either tyrosine (420 µg kg −1 BW), DT (420 µg kg −1 BW), or lycopene at high (10 mg kg −1 BW) and low (5 mg kg −1 BW) doses for 35 days. Lycopene administration effectively reduced oxidative stress, cardiac fatty acid accumulation, and cardiac hypertrophy and improved mitochondrial performance in DT-induced mice. In vitro experiments in H9c2 cells showed that DT directly inhibited the activity of the respiratory chain complex, whereas oxidative phosphorylation and 𝜷-oxidation gene expression is upregulated. Lycopene enhanced the activity of the complexes and inhibited ROS production caused by compensatory regulation. Conclusion: Lycopene improves DT-mediated myocardial energy homeostasis disorder by promoting the activity of respiratory chain complexes I and IV and alleviates the accumulation of cardiac fatty acids and myocardial hypertrophy.

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Lycopene Inhibits Oxidative Stress-Mediated Inflammatory Responses in Ethanol/Palmitoleic Acid-Stimulated Pancreatic Acinar AR42J Cells

Cited by 29 publications

References 44 publications

Astaxanthin Inhibits Interleukin-6 Expression in Cerulein/Resistin-Stimulated Pancreatic Acinar Cells

Astaxanthin Inhibits Interleukin-6 Expression in Cerulein/Resistin-Stimulated Pancreatic Acinar Cells

Lycopene Inhibits Toll-Like Receptor 4-Mediated Expression of Inflammatory Cytokines in House Dust Mite-Stimulated Respiratory Epithelial Cells

Lycopene Regulates Dietary Dityrosine‐Induced Mitochondrial‐Lipid Homeostasis by Increasing Mitochondrial Complex Activity

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