title: [Effect of WS070117M1 on chronic obstructive pulmonary disease in mice and the underling mechanisms of anti-inflammation].
abstract: The aim of this study is to investigate the anti-inflammatory effect of the adenosine derivative N6-(3-hydroxylaniline) adenosine (WS070117M1) on cigarette smoke plus LPS (lipopolysaccharide)-induced chronic obstructive pulmonary disease (COPD) in mice and its mechanism. COPD model was established by exposing male BALB/c mice to cigarette smoke and challenged with LPS inhalation. Supernatants of bronchoalveolar lavage fluid (BALF) were harvested and IL-1β, IL-6, IL-8 and TGF-β1 levels were measured by ELISA (enzyme-linked immunesorbent assay). The number of total white blood cells and neutrophils in bronchoalveolar lavage fluid was counted separately. Lung tissue was stained with Mayer 's hematoxylin and eosin for histopathologic examination. pAMPKa protein expression and distribution of lung tissue were analyzed by immunohistochemistry method. In vitro, levels of AMPKα phosphorylation in phorbol-12- myristate-13-acetate (PMA) differentiated THP-1 cells was detected by immunohistochemistry, IL-8 level in supernatants of cigarette smoke condensate stimulating PMA differentiated THP-1 cells was measured by ELISA. The results showed that WS070117M1 treatment significantly activated AMPKa in the lung tissue. It also resulted in down regulation of IL-1β, IL-6, IL-8 and TGF-β1 levels in bronchoalveolar lavage fluid and IL-8 level in cigarette smoke condensate stimulating PMA differentiated THP-1 cells. In addition, WS070117M1 could inhibit the recruitment of total white blood cells and neutrophils. These results suggest that WS070117M1 may alleviate the airway inflammation by activating AMPK in the lung tissue.
authors.forename: Shu-hua
authors.initials: SH
authors.lastname: Cao
authors.forename: Ling-ling
authors.initials: LL
authors.lastname: Xuan
authors.forename: Dong-mei
authors.initials: DM
authors.lastname: Wang
authors.forename: Jian-lin
authors.initials: JL
authors.lastname: Xie
authors.forename: Ren-tao
authors.initials: RT
authors.lastname: Jiang
authors.forename: Jin-ye
authors.initials: JY
authors.lastname: Bai
authors.forename: Song
authors.initials: S
authors.lastname: Wu
authors.forename: Qi
authors.initials: Q
authors.lastname: Hou
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000241:Adenosine / Q000031:analogs & derivatives*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D006801:Humans; D007249:Inflammation / Q000188:drug therapy*; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D007958:Leukocyte Count; D008070:Lipopolysaccharides; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009504:Neutrophils / Q000166:cytology; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy*; D012906:Smoke / Q000009:adverse effects; D014026:Nicotiana; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: C587672:IL1B protein, mouse; D053583:Interleukin-1beta; D015850:Interleukin-6; D016209:Interleukin-8; D008070:Lipopolysaccharides; D012906:Smoke; C508961:Tgfb1 protein, mouse; D053773:Transforming Growth Factor beta1; D055372:AMP-Activated Protein Kinases; D000241:Adenosine