title: [Lipid derivative of benzylidene malononitrile AG490 attenuates airway inflammation of mice with neutrophilic asthma].
abstract: Objective To observe the effect of lipid derivative of benzylidene malononitrile AG490 on the airway inflammation in a mouse model of neutrophilic asthma (NA). Methods Fifty-four specific pathogen-free (SPF) female C57BL/6 mice were randomly divided into 3 groups: NA group, AG490-treated NA (NAAG) group, and normal control (NC) group, 18 mice in each group. The NA group and the NAAG group were sensitized by airway instillation of ovalbumin (OVA) and lipopolysaccharide (LPS) on day 0, 6 and 13. The NAAG group was injected with AG490 (500 μg/mouse, i.p.) three times a week, from day 0 after the first sensitization, for 3 weeks. Mice were challenged on day 21, 22 for 1 hour/time with an aerosol of 10 g/L OVA. At 24 hours after the final challenge, bronchoalveolar lavage fluid (BALF) was collected. The total number and differential counts of nucleated cells and the percentage of each type were determined. HE staining and PAS staining was employed for observing the lung pathological changes. The percentages of Th17 cells and regulatory T cells (Treg) in the lung issue were determined by flow cytometry. The level of interleukin-17 (IL-17) in BALF was measured using ELISA. Results Compared with the NA group, the total number of nucleated cells, the percentage of neutrophils and the percentage of eosinophils in BALF in the NAAG group were obviously reduced; lung tissue pathologic changes were improved in the NAAG group; goblet cell hyperplasia and the level of IL-17 in BALF in the NAAG group were significantly down-regulated; the proportion of Treg in the lung increased and the proportion of Th17 cells in the lung decreased in the NAAG group. Conclusion After NA mice are treated with AG490 during the sensitization phase, the proportion of Treg in the lung would increase and the proportion of Th17 cells in the lung would decrease. AG490 could attenuate the airway inflammation in the mouse model of NA.
authors.affiliation: Department of Pediatrics, First Affiliated Hospital, Guangxi Medical University, Nanning 530021, China.
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Pediatrics, First Affiliated Hospital, Guangxi Medical University, Nanning 530021, China. *Corresponding author, E-mail: ngm8525@163.com.
authors.forename: Guangmin
authors.initials: G
authors.lastname: Nong
authors.affiliation: Department of Pediatrics, First Affiliated Hospital, Guangxi Medical University, Nanning 530021, China.
authors.forename: Min
authors.initials: M
authors.lastname: Jiang
authors.affiliation: Department of Pediatrics, First Affiliated Hospital, Guangxi Medical University, Nanning 530021, China.
authors.forename: Wenjie
authors.initials: W
authors.lastname: Zhan
mesh_terms: D000818:Animals; D001249:Asthma / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology / Q000276:immunology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005434:Flow Cytometry; D007249:Inflammation / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D020381:Interleukin-17 / Q000276:immunology / Q000378:metabolism; D008055:Lipids / Q000737:chemistry; D008070:Lipopolysaccharides / Q000276:immunology; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism; D010047:Ovalbumin / Q000276:immunology; D011897:Random Allocation; D012137:Respiratory System / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D058504:Th17 Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D020032:Tyrphostins / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D020381:Interleukin-17; D008055:Lipids; D008070:Lipopolysaccharides; D020032:Tyrphostins; C095512:alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide; D010047:Ovalbumin