Journal
FREE RADICAL BIOLOGY AND MEDICINE
Volume 69, Issue -, Pages 208-218Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.freeradbiomed.2014.01.026
Keywords
Glucosamine; Cigarette smoke; Lung inflammation; NADPH oxidase; Reactive oxygen species; AMP-activated protein kinase; Mitogen-activated protein kinases; NF-kappa B; SAT3; Free radicals
Funding
- National Science Council, Taiwan [NSC 101-2320-B-010-042-MY3, NSC 100-2628-B-001-MY2, NSC 102-2628-B-010-001-MY3, NSC 100-2320-B-010-018-MY3]
- Mackay Memorial Hospital, Taipei, Taiwan [MMH10193]
- Ministry of Education, Aim for the Top University Plan, Taiwan
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Cigarette smoking causes persistent lung inflammation that is mainly regulated by redox-sensitive pathways. We have reported that cigarette smoke (CS) activates a NADPH oxidase-dependent reactive oxygen species (ROS)-sensitive AMP-activated protein kinase (AMPK) signaling pathway leading to induction of lung inflammation. Glucosamine, a dietary supplement used to treat osteoarthritis, has antioxidant and anti-inflammatory properties. However, whether glucosamine has similar beneficial effects against CS-induced lung inflammation remains unclear. Using a murine model we show that chronic CS exposure for 4 weeks increased lung levels of 4-hydroxynonenal (an oxidative stress biomarker), phospho-AMPK, and macrophage inflammatory protein 2 and induced lung inflammation; all of these CS-induced events were suppressed by chronic treatment with glucosamine. Using human bronchial epithelial cells, we demonstrate that cigarette smoke extract (CSE) sequentially activated NADPH oxidase; increased intracellular levels of ROS; activated AMPK, mitogen-activated protein kinases (MAPKs), nuclear factor-kappa B (NF-kappa B), and signal transducer and activator of transcription proteins 3 (STAT3); and induced interleukin-8 (IL-8). Additionally, using a ROS scavenger, a siRNA that targets AMPK, and various pharmacological inhibitors, we identified the signaling cascade that leads to induction of IL-8 by CSE. All these CSE-induced events were inhibited by glucosamine pretreatment. Our findings suggest a novel role for glucosamine in alleviating the oxidative stress and lung inflammation induced by chronic CS exposure in vivo and in suppressing the CSE-induced IL-8 in vitro by inhibiting both the ROS-sensitive NADPH oxidase/AMPK/MAPK signaling pathway and the downstream transcriptional factors NF-kappa B and STAT3. (c) 2014 Elsevier Inc. All rights reserved.
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