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Free Radic Biol Med. 2014 Apr;69:208-18. doi: 10.1016/j.freeradbiomed.2014.01.026. Epub 2014 Jan 28.

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

Author information

1
Department of Physiology, School of Medicine, National Yang-Ming University, Taipei 112, Taiwan.
2
Division of Thoracic Surgery, Mackay Memorial Hospital, Taipei, Taiwan; Department of Cosmetic Applications and Management, Mackay Medicine, Nursing and Management College, Taipei, Taiwan.
3
Division of Thoracic Surgery, Mackay Memorial Hospital, Taipei, Taiwan; Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, Taipei 112, Taiwan.
4
Department of Physiology, School of Medicine, National Yang-Ming University, Taipei 112, Taiwan. Electronic address: tslee@ym.edu.tw.
5
Department of Physiology, School of Medicine, National Yang-Ming University, Taipei 112, Taiwan. Electronic address: yrkou@ym.edu.tw.

Abstract

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-κB (NF-κB), 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-κB and STAT3.

KEYWORDS:

AMP-activated protein kinase; Cigarette smoke; Free radicals; Glucosamine; Lung inflammation; Mitogen-activated protein kinases; NADPH oxidase; NF-κB; Reactive oxygen species; SAT3

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