Regulation of pro-inflammatory responses by lipoxygenases via intracellular reactive oxygen species in vitro and in vivo.
10.3858/emm.2008.40.4.461
- Author:
So Yong KIM
1
;
Tae Bum KIM
;
Keun Ai MOON
;
Tae Jin KIM
;
Dongwoo SHIN
;
You Sook CHO
;
Hee Bom MOON
;
Ki Young LEE
Author Information
1. Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon, Korea. thylee@med.skku.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
anti-inflammatory agents;
asthma;
lipoxygenase;
macrophages;
models, animal;
NF-kappa B;
reactive oxygen species
- MeSH:
Animals;
Antioxidants/metabolism;
Asthma/complications/metabolism/pathology/physiopathology;
Bronchial Hyperreactivity/drug therapy/pathology;
Bronchial Provocation Tests;
Bronchoalveolar Lavage Fluid/cytology;
Cells, Cultured;
Drug Evaluation, Preclinical;
Humans;
Inflammation/*etiology/metabolism;
Jurkat Cells;
Lipoxygenase/*physiology;
Lipoxygenase Inhibitors/pharmacology/therapeutic use;
Lymphocytes/drug effects/metabolism;
Male;
Mice;
Mice, Inbred BALB C;
Nordihydroguaiaretic Acid/pharmacology/therapeutic use;
Reactive Oxygen Species/*adverse effects/*metabolism
- From:Experimental & Molecular Medicine
2008;40(4):461-476
- CountryRepublic of Korea
- Language:English
-
Abstract:
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-alpha, IL-1beta, and LPS resulted in significant ROS production and NF-kappaB 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-alpha 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.
