Regulation of pro-inflammatory responses by lipoxygenases via intracellular reactive oxygen species in vitro and in vivo

• Published in: Experimental & molecular medicine 2008, 40(4), , pp.461-476
• Main Authors: Kim, So Yong, Kim, Tae-Bum, Moon, Keun-ai, Kim, Tae Jin, Shin, Dongwoo, Cho, You Sook, Moon, Hee-Bom, Lee, Ki-Young
• Format: Article
• Language: English
• Subjects: Animals; Antioxidants - metabolism; Asthma - complications; Asthma - metabolism; Asthma - pathology; Asthma - physiopathology; Biomedical and Life Sciences; Biomedicine; Bronchial Hyperreactivity - drug therapy; Bronchial Hyperreactivity - pathology; Bronchial Provocation Tests; Bronchoalveolar Lavage Fluid - cytology; Cells, Cultured; Drug Evaluation, Preclinical; Humans; Inflammation - etiology; Inflammation - metabolism; Jurkat Cells; Lipoxygenase - physiology; Lipoxygenase Inhibitors - pharmacology; Lipoxygenase Inhibitors - therapeutic use; Lymphocytes - drug effects; Lymphocytes - metabolism; Male; Masoprocol - pharmacology; Masoprocol - therapeutic use; Medical Biochemistry; Mice; Mice, Inbred BALB C; Molecular Medicine; Original; Reactive Oxygen Species - adverse effects; Reactive Oxygen Species - metabolism; Stem Cells; 생화학
• ISSN: 1226-3613; 2092-6413
• DOI: 10.3858/emm.2008.40.4.461

Reactive oxygen species (ROS) performs a pivotal function as a signaling mediator in receptor-mediated signaling. However, the sources of ROS in this signaling have yet to be determined, but may include lipoxygenases (LOXs) and NADPH oxidase. The stimulation of lymphoid cells with TNF-α, IL-1β, and LPS resulted in significant ROS production and NF-κB activation. Intriguingly, these responses were markedly abolished via treatment with the LOXs inhibitor nordihydroguaiaretic acid (NDGA). We further examined in vivo anti-inflammatory effects of NDGA in allergic airway inflammation. Both intraperitoneal and intravenous NDGA administration attenuated ovalbumin (OVA)-induced influx into the lungs of total leukocytes, as well as IL-4, IL-5, IL-13, and TNF-α levels. NDGA also significantly reduced serum levels of OVA-specific IgE and suppressed OVA-induced airway hyperresponsiveness to inhaled methacholine. The results of our histological studies and flow cytometric analyses showed that NDGA inhibits OVA-induced lung inflammation and the infiltration of CD11b + macrophages into the lung. Collectively, our findings indicate that LOXs performs an essential function in pro-inflammatory signaling via the regulation of ROS regulation, and also that the inhibition of LOXs activity may have therapeutic potential with regard to the treatment of allergic airway inflammation.