Jingjing Wei1, Hui Zhao2, Guoquan Fan3, Jianqiang Li4. 1. Department of Pediatrics, Shanxi Medical University, Taiyuan 030001, China; Department of Respiratory Medicine, Shanxi Medical University Second Hospital, Taiyuan 030001, China. 2. Department of Respiratory Medicine, Shanxi Medical University Second Hospital, Taiyuan 030001, China. 3. Teaching and Research Office of Microbiology & Immunology, Shanxi Medical University, Taiyuan 030001, China. 4. Department of Respiratory Medicine, Shanxi Medical University Second Hospital, Taiyuan 030001, China. Electronic address: ljqhx@sina.com.
Abstract
BACKGROUND: Cigarette smoking is a significant risk factor for emphysema, which is characterized by airway inflammation and oxidative damage. OBJECTIVES: To assess the capacity of bilirubin to protect against smoke-induced emphysema. METHODS: Smoking status and bilirubin levels were recorded in 58 patients with chronic obstructive pulmonary diseases (COPD) and 71 non-COPD participants. The impact of smoking on serum bilirubin levels and exogenous bilirubin (20 mg/kg/day) on pulmonary injury was assessed in a rat model of smoking-induced emphysema. At sacrifice lung histology, airway leukocyte accumulation and cytokine and chemokine levels in serum, bronchoalveolar lavage fluid (BALF) and lung were analyzed. Oxidative lipid damage and anti-oxidative components was assessed by measuring malondialdehyde, superoxide dismutase (SOD) activity and glutathione. RESULTS: Total serum bilirubin levels were lower in smokers with or without COPD than non-smoking patients without COPD (P < 0.05). Indirect serum bilirubin levels were lower in COPD patients than patients without COPD (P < 0.05). In rats, cigarette smoke reduced serum total and indirect bilirubin levels. Administration of bilirubin reduced mean linear intercept and mean alveoli area, increased mean alveoli number, reduced macrophage, neutrophil and TNF-α content of BALF, and increased BALF and serum IL-10 level, but lowered local and systemic CCL2, CXCL2, CXCL8 and IL-17 levels. Bilirubin suppressed the smoke-induced systemic and regional oxidative lipid damage associated with increased SOD activity. CONCLUSION: Bilirubin attenuated smoking-induced pulmonary injury by suppressing inflammatory cell recruitment and pro-inflammatory cytokine secretion, increasing anti-inflammatory cytokine levels, and anti-oxidant SOD activity in a rat model of smoke-induced emphysema.
BACKGROUND: Cigarette smoking is a significant risk factor for emphysema, which is characterized by airway inflammation and oxidative damage. OBJECTIVES: To assess the capacity of bilirubin to protect against smoke-induced emphysema. METHODS: Smoking status and bilirubin levels were recorded in 58 patients with chronic obstructive pulmonary diseases (COPD) and 71 non-COPDparticipants. The impact of smoking on serum bilirubin levels and exogenous bilirubin (20 mg/kg/day) on pulmonary injury was assessed in a rat model of smoking-induced emphysema. At sacrifice lung histology, airway leukocyte accumulation and cytokine and chemokine levels in serum, bronchoalveolar lavage fluid (BALF) and lung were analyzed. Oxidative lipid damage and anti-oxidative components was assessed by measuring malondialdehyde, superoxide dismutase (SOD) activity and glutathione. RESULTS: Total serum bilirubin levels were lower in smokers with or without COPD than non-smoking patients without COPD (P < 0.05). Indirect serum bilirubin levels were lower in COPDpatients than patients without COPD (P < 0.05). In rats, cigarette smoke reduced serum total and indirect bilirubin levels. Administration of bilirubin reduced mean linear intercept and mean alveoli area, increased mean alveoli number, reduced macrophage, neutrophil and TNF-α content of BALF, and increased BALF and serum IL-10 level, but lowered local and systemic CCL2, CXCL2, CXCL8 and IL-17 levels. Bilirubin suppressed the smoke-induced systemic and regional oxidative lipid damage associated with increased SOD activity. CONCLUSION:Bilirubin attenuated smoking-induced pulmonary injury by suppressing inflammatory cell recruitment and pro-inflammatory cytokine secretion, increasing anti-inflammatory cytokine levels, and anti-oxidant SOD activity in a rat model of smoke-induced emphysema.
Authors: Ah Young Leem; Young Sam Kim; Ji-Hyun Lee; Tae-Hyung Kim; Ha Yan Kim; Yeon Mok Oh; Sang Do Lee; Ji Ye Jung Journal: Respir Res Date: 2019-12-09