Saturated Fatty Acid Increases Lung Macrophages and Augments House Dust Mite-Induced Airway Inflammation in Mice Fed wit
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ORIGINAL ARTICLE
Saturated Fatty Acid Increases Lung Macrophages and Augments House Dust Mite-Induced Airway Inflammation in Mice Fed with High-Fat Diet Hiroki Tashiro,1 Koichiro Takahashi ,1,3 Hironori Sadamatsu,1 Go Kato,1 Keigo Kurata,2 Shinya Kimura,1 and Naoko Sueoka-Aragane1
Abstract—Obesity is one of the phenotypes of severe asthma, which is considered to be a heterogeneous syndrome; however, its interaction with airway inflammation is not fully understood. The aim of this study was to clarify the role of saturated fatty acids in augmenting airway inflammation induced by house dust mite (HDM) in obesity. Subjects were Balb/c mice fed a high-fat diet (HFD) for 10 weeks, followed by sensitization and exposure to HDM. Subjects were also administered palmitic acid (PA) for 4 weeks with concurrent sensitization and exposure to HDM. Airway inflammation was assessed by quantifying the amount of inflammatory cells in bronchoalveolar lavage (BAL) and airway resistance was measured. In vitro, lipopolysaccharide (LPS)-primed macrophages were stimulated by PA. The amount of monocyte chemoattractant protein-1 (MCP-1), interleukin-1β (IL-1β), and tumor necrosis factor α (TNF-α) was examined in the supernatant. Compared to normal chow mice, HFD mice underwent significant increases in body weight; increases in number of lung macrophages, including circulating monocytes and alveolar macrophages; and increases in bronchoalveolar lavage fluid (BALF) total cell count, including neutrophils but not eosinophils, after HDM sensitization and exposure. In vitro, PA induced MCP-1 and augmented LPS-primed production of IL-1β and TNF-α in macrophages. Among HDM mice that were administered PA, there was an increase BALF total cell count, including neutrophils but not eosinophils, compared to vehicle mice. In conclusion, saturated fatty acid increased the number of lung macrophages and augmented HDM-induced neutrophilic airway inflammation in a HFD mouse model. KEY WORDS: bronchial asthma; obesity; high-fat diet; house dust mite; saturated fatty acid; macrophages.
INTRODUCTION Bronchial asthma is a common respiratory disease that involves eosinophilic airway inflammation induced by sensitization and exposure to antigens, such 1
Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga, 849-8501, Japan 2 Institute of Tokyo Environmental Allergy, Tokyo, Japan 3 To whom correspondence should be addressed at Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga, 8498501, Japan. E-mail: [email protected]
as house dust mite (HDM) [14, 23]. Inhaled corticosteroid (ICS), which is the principal medication for the treatment of asthma, has contributed to disease control and reduction of mortality for the past 20 years [47]. However, 5% to 10% of cases that are refractory to standard treatment are identified as severe asthma [8, 27, 35]. Severe asthm
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