Progressive inflammation and fibrosis are the central processes in the pathogenesis of pulmonary fibrosis. It is believed that macrophages in areas of chronically inflamed lung play a key role in fibrotic response. Th...Progressive inflammation and fibrosis are the central processes in the pathogenesis of pulmonary fibrosis. It is believed that macrophages in areas of chronically inflamed lung play a key role in fibrotic response. Therefore, we investigated the effects of alveolar macrophage (AmΦ) conditioned media from interstitial lung disease (ILD) patients on lung fibroblast proliferation and procollagen mRNA expression. After stimulating with AmΦ conditioned media from ILD patients, the fibroblast proliferation increased 71. 4 % compared with the control, but for media from bronchial carcinoma (BC) patients, it just increased 14. 3%. There is a significant difference between the two groups (P<0. 05). The procollagen a1 (Ⅰ) mRNA in fibroblasts stimulated with AmΦ conditioned media from ILD patients was increased 21. 3 %, and a1 ( Ⅲ) was 37. 2% higher than control (P<0.05). It increased 6. 8% and 12. 8% for media from BC patients respectively, but there was no difference when compared to the control. We considered that AmΦ from ILD patients might be in an activated state and could release some growth factors to stimulate fibroblast proliferation and promote collagen DNA expression.展开更多
OBJECTIVE: To investigate the effect of Chaiqinchengqi decoction(CQCQD) on inositol requiring enzyme 1α(IRE1α) in alveolar macrophages(AMs)of the dog model of acute necrotising pancreatitis(ANP) induced by sodium ta...OBJECTIVE: To investigate the effect of Chaiqinchengqi decoction(CQCQD) on inositol requiring enzyme 1α(IRE1α) in alveolar macrophages(AMs)of the dog model of acute necrotising pancreatitis(ANP) induced by sodium taurocholate.METHODS: Fifteen beagle dogs were randomised into a control group,ANP group and CQCQD group(n = 5 per group). ANP was induced by a retrograde duct injection of 50 mg/kg of 5% sodium taurocholate. The dogs in the control group received injections of the same volume of saline as the sodium taurocholate. After the models were induced,the dogs in the CQCQD group were administered 10 m L/kg CQCQD every 2 h for 6 h. Two hours after the last administration of either CQCQD or saline,they were sacrificed by anaesthesia. AMs were collected to determine the IRE1α and Interleukin-1β(IL-1β)m RNA and protein expression,and pancreatic tissues were collected for histopathology analysis.RESULTS: Compared with the ANP group,the m RNA and protein expression of IRE1α and the protein expression of IL-1β of AMs in the CQCQD group were significantly down-regulated,and the pancreatic histopathology score of the CQCQD group also was lower. There was no significant difference in the m RNA expression of IL-1β of AMs between the two groups.CONCLUSION: The CQCQD-induced down-regulation of the IL-1β protein expression may involve the down-regulation of the m RNA and protein expression of IRE1α in AMs.展开更多
CD1d-restricted natural killer T(NKT)cells are innate-like T lymphocytes with protective or pathogenic roles in the development of influenza pneumonia.Here,we show that lung-infiltrated and activated NKT cells are the...CD1d-restricted natural killer T(NKT)cells are innate-like T lymphocytes with protective or pathogenic roles in the development of influenza pneumonia.Here,we show that lung-infiltrated and activated NKT cells are the major cellular source of LIGHT/TNFSF14,which determines the severity of pulmonary pneumonia by highly deteriorative influenza A virus(IAV)infection.Compared to wild-type mice,LIGHT^(-/-)mice exhibit much lower morbidity and mortality to IAV,due to alleviated lung damage and reduced apoptosis of alveolar macrophages(AMs).LIGHT preferentially promotes cell death of lymphotoxin β receptors positive(LTβR^(+))AMs but not herpesvirus entry mediator positive(HVEM^(+))AMs.Therefore,these results suggest that NKT-derived LIGHT augments cell death of the tissue protective AMs in exacerbating lung pathology and susceptibility to fatal influenza infection.Suppression of LIGHT signaling might be a viable option in the treatment of influenza-associated acute respiratory distress syndrome.展开更多
文摘Progressive inflammation and fibrosis are the central processes in the pathogenesis of pulmonary fibrosis. It is believed that macrophages in areas of chronically inflamed lung play a key role in fibrotic response. Therefore, we investigated the effects of alveolar macrophage (AmΦ) conditioned media from interstitial lung disease (ILD) patients on lung fibroblast proliferation and procollagen mRNA expression. After stimulating with AmΦ conditioned media from ILD patients, the fibroblast proliferation increased 71. 4 % compared with the control, but for media from bronchial carcinoma (BC) patients, it just increased 14. 3%. There is a significant difference between the two groups (P<0. 05). The procollagen a1 (Ⅰ) mRNA in fibroblasts stimulated with AmΦ conditioned media from ILD patients was increased 21. 3 %, and a1 ( Ⅲ) was 37. 2% higher than control (P<0.05). It increased 6. 8% and 12. 8% for media from BC patients respectively, but there was no difference when compared to the control. We considered that AmΦ from ILD patients might be in an activated state and could release some growth factors to stimulate fibroblast proliferation and promote collagen DNA expression.
基金Supported by the National Natural Science Foundation of China(the Mechanism of Protein Molecular Brake of Suppression the Releasing of Pro-Inflammatory Cytokines of Macrophage in Acute Necrotizing Pancreatitis by Chaiqinchengqi Decoction,No.81072910)Science and Technology Support Program of Sichuan(Effect of Chaiqincheng Decoction on the Gastrointestinal Dysfunction in Severe Acute Pancreatitis and the Establishment of Evaluation System,No.2014SZ0211)
文摘OBJECTIVE: To investigate the effect of Chaiqinchengqi decoction(CQCQD) on inositol requiring enzyme 1α(IRE1α) in alveolar macrophages(AMs)of the dog model of acute necrotising pancreatitis(ANP) induced by sodium taurocholate.METHODS: Fifteen beagle dogs were randomised into a control group,ANP group and CQCQD group(n = 5 per group). ANP was induced by a retrograde duct injection of 50 mg/kg of 5% sodium taurocholate. The dogs in the control group received injections of the same volume of saline as the sodium taurocholate. After the models were induced,the dogs in the CQCQD group were administered 10 m L/kg CQCQD every 2 h for 6 h. Two hours after the last administration of either CQCQD or saline,they were sacrificed by anaesthesia. AMs were collected to determine the IRE1α and Interleukin-1β(IL-1β)m RNA and protein expression,and pancreatic tissues were collected for histopathology analysis.RESULTS: Compared with the ANP group,the m RNA and protein expression of IRE1α and the protein expression of IL-1β of AMs in the CQCQD group were significantly down-regulated,and the pancreatic histopathology score of the CQCQD group also was lower. There was no significant difference in the m RNA expression of IL-1β of AMs between the two groups.CONCLUSION: The CQCQD-induced down-regulation of the IL-1β protein expression may involve the down-regulation of the m RNA and protein expression of IRE1α in AMs.
基金supported by the Chinese Academy of Sciences(XDB29030301)the Ministry of Science and Technology(2018ZX10101004002004 and 2018YFC1200703)the National Natural Science Foundation of China(31321001,31621061,81590764,and 31400755)。
文摘CD1d-restricted natural killer T(NKT)cells are innate-like T lymphocytes with protective or pathogenic roles in the development of influenza pneumonia.Here,we show that lung-infiltrated and activated NKT cells are the major cellular source of LIGHT/TNFSF14,which determines the severity of pulmonary pneumonia by highly deteriorative influenza A virus(IAV)infection.Compared to wild-type mice,LIGHT^(-/-)mice exhibit much lower morbidity and mortality to IAV,due to alleviated lung damage and reduced apoptosis of alveolar macrophages(AMs).LIGHT preferentially promotes cell death of lymphotoxin β receptors positive(LTβR^(+))AMs but not herpesvirus entry mediator positive(HVEM^(+))AMs.Therefore,these results suggest that NKT-derived LIGHT augments cell death of the tissue protective AMs in exacerbating lung pathology and susceptibility to fatal influenza infection.Suppression of LIGHT signaling might be a viable option in the treatment of influenza-associated acute respiratory distress syndrome.
