The immunomodulation of endotoxin-induced acute lung injury by hesperidin in vivo and in vitro |
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Authors: | Yeh Chia-Chou Kao Shang-Jyh Lin Chih-Che Wang Shulhn-Der Liu Ching-Ju Kao Shung-Te |
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Affiliation: | a Institute of Chinese Medical Science, College of Chinese Medicine, China Medical University, Taichung, Taiwan b School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan c Department of Chinese Medicine, Buddhist Dalin Tzu Chi General Hospital, Chiayi, Taiwan d Division of Internal Medicine, Shih Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan e Department of Chinese Medicine, China Medical University hospital, Taichung, Taiwan |
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Abstract: | To investigate the modulation of lung local immune responses of hesperidin (HES) on the acute lung inflammation induced by LPS in vivo. Mice were challenged with intratracheal lipopolysaccharide (100 μg) 30 min before with treatment hesperidin (200 mg/kg oral administration) or vehicle. After 4 and 24 h, bronchoalveolar lavage fluid was obtained to measure proinflammatory (TNF-α, IL-1β, IL-6), anti-inflammatory (IL-10, IL-4, IL-12) cytokines, chemokines (KC, MCP-1 and MIP-2), total cell counts, nitric oxide production, and proteins. Lung histology was performed in inflated-fixed lungs. Hesperidin downregulate the LPS-induced expression of TNF-α, IL-1β, IL-6, KC, MIP-2, MCP-1, and IL-12. It also enhanced the production of IL-4, IL-10. Total leukocyte counts; nitric oxide production, iNOS expression, and proteins were significantly decreased by hesperidin. In vitro, HES suppressed the expression of IL-8 on A549 cells and THP-1 cells, the expression of TNF-α, IL-1β, and IL-6 on THP-1 cells, the expression of ICAM-1 and VCAM-1 on A549 cells which effect cell adhesion function. The suppression of those molecules is controlled by NF-κB and AP-1, which are activated by IκB and MAPK pathways. HES inhibits those pathways, thereby suppressing the expression of IL-8, TNFα, IL-1β, IL-6, IL-12, ICAM-1 and VCAM-1. This study indicates that HES had a markedly immunomodulatory effect in a clinically relevant model of ARDS. Nevertheless, further investigations are required to determine the potential clinical usefulness of HES in the adjunctive therapy of ARDS. |
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Keywords: | LPS Proinflammatory cytokines Anti-inflammatory cytokines Chemokines Immunomodulation ICAM-1 VCAM-1 |
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