SMAD-signaling in chronic obstructive pulmonary disease: transcriptional down-regulation of inhibitory SMAD 6 and 7 by cigarette smoke

2004 ◽  
Vol 385 (7) ◽  
Author(s):  
J. Springer ◽  
F.R. Scholz ◽  
C. Peiser ◽  
D.A. Groneberg ◽  
A. Fischer
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Cigarette Smoke ◽  
Tobacco Smoke ◽  
Airway Remodeling ◽  
Chronic Obstructive ◽  
Volatile Components ◽  
Down Regulation ◽  
Obstructive Pulmonary Disease ◽  
Smad Signaling

AbstractTransforming growth factor-β1 is a potent mediator of fibrosis stimulating the secretion of extracellular matrix proteins and is involved in airway remodeling in chronic obstructive pulmonary disease (COPD). Signals from the TGF superfamily are mediated by the SMAD group of transcription factors. Here, the expression of the regulatory SMAD2, 3, the co-SMAD4 and the inhibitory SMAD6 and 7 was assessed in bronchial biopsies of COPD patients and controls by quantitative RTPCR. While SMAD2 was not expressed and SMAD3 and 4 displayed no change, the inhibitory SMAD6 and 7 were significantly downregulated in COPD. To reveal the molecular basis of tobacco smoke-induced airway remodeling and to test whether it may interfere with intracellular SMAD signaling, the airway epithelial cell line A549 was incubated with cigarette smoke extract (1% and 10%) for 48 hours, which led to down-regulation of SMAD6 and 7 at both concentrations tested. It can be concluded that TGF-β-mediated effects in COPD are influenced by a disturbed intracellular feedback mechanism of inhibitory SMADs. Also, the effects of non-volatile components in tobacco smoke may partly be regulated via a smoke-induced down-regulation of inhibitory SMADs.

scholarly journals Yijin-Tang Attenuates Cigarette Smoke and Lipopolysaccharide-Induced Chronic Obstructive Pulmonary Disease in Mice

2022 ◽  
Vol 2022 ◽  
pp. 1-12
Author(s):  
Jinhyung Rho ◽  
Chang-Seob Seo ◽  
Eun-Ju Hong ◽  
Eun Bok Baek ◽  
Eunhye Jung ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Cigarette Smoke ◽  
Transforming Growth Factor ◽  
Airway Remodeling ◽  
Interleukin 1 ◽  
Chronic Obstructive ◽  
Necrosis Factor Alpha ◽  
Obstructive Pulmonary Disease ◽  
Cell Counts

Background. Chronic obstructive pulmonary disease (COPD) refers to a lung disorder associated with symptoms of dyspnea, cough, and sputum production. Traditionally, Yijin-tang (YJT), a mixture of Pinellia ternate, Poria cocos, ginger, Chinese liquorice, and tangerine peel, has been prescribed for the treatment of respiratory system diseases caused by dampness phlegm. This experiment investigated the therapeutic effect of YJT in a mouse model of cigarette smoke (CS)- and lipopolysaccharide (LPS)-induced COPD. Methods. COPD was induced by exposing mice to CS for 1 hour per day for 8 weeks, with intranasal delivery of LPS on weeks 1, 3, 5, and 7. YJT was administered at doses of 100 and 200 mg/kg 1 hour before CS exposure for the last 4 weeks. Results. YJT significantly suppressed CS- and LPS-induced increases in inflammatory cell counts and reduced interleukin-1 beta (IL-1β), IL-6, tumor necrosis factor-alpha (TNF-α), and monocyte chemoattractant protein-1 (MCP-1) levels in bronchoalveolar lavage fluid (BALF) and lung tissue. In addition, YJT not only decreased airway wall thickness, average alveolar intercept, and lung fibrosis, but it also suppressed the expression of matrix metallopeptidase (MMP)-7, MMP-9, and transforming growth factor-B (TGF-β) and collagen deposition. Moreover, YJT suppressed phosphorylation of nuclear factor-kappa B (NF-κB) as well as expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). Conclusion. Collectively, our findings show that YJT attenuates respiratory inflammation and airway remodeling caused by CS and LPS exposure; therefore, therapeutic applications in COPD can be considered.

scholarly journals Protective effect of Palmijihwanghwan in a mouse model of cigarette smoke and lipopolysaccharide-induced chronic obstructive pulmonary disease

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Eun Bok Baek ◽  
Jin-hyung Rho ◽  
Eunhye Jung ◽  
Chang-Seob Seo ◽  
Jin-Hee Kim ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Mouse Model ◽  
Protective Effect ◽  
Pulmonary Disease ◽  
Cigarette Smoke ◽  
Transforming Growth Factor ◽  
Airway Remodeling ◽  
Interleukin 1 ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease

Abstract Background Palmijihwanghwan (PJH) is a traditional medicine and eight constituents derived from PJH possess anti-inflammatory activities. However, the scientific evidence for its potential as a therapeutic agent for inflammatory lung disease has not yet been studied. In this study, we examined the protective effect of PJH in a mouse model of chronic obstructive pulmonary disease (COPD) induced by cigarette smoke (CS) with lipopolysaccharide (LPS). Methods Mice received CS exposure for 8 weeks and intranasal instillation of LPS on weeks 1, 3, 5 and 7. PJH (100 and 200 mg/kg) was administrated daily 1 h before CS treatment for the last 4 weeks. Results Compared with CS plus LPS-exposed mice, mice in the PJH-treated group showed significantly decreased inflammatory cells count and reduced inflammatory cytokines including interleukin-1 beta (IL-1β), IL-6 and tumor necrosis factor alpha (TNF-α) levels in broncho-alveolar lavage fluid (BALF) and lung tissue. PJH also suppressed the phosphorylation of nuclear factor kappa B (NF-κB) and extracellular signal-regulated kinase1/2 (ERK1/2) caused by CS plus LPS exposure. Furthermore, CS plus LPS induced increases in matrix metallopeptidase (MMP)-7, MMP-9, and transforming growth factor-β (TGF-β) expression and collagen deposition that were inhibited in PJH-treated mice. Conclusions This study demonstrates that PJH prevents respiratory inflammation and airway remodeling caused by CS with LPS exposure suggesting potential therapy for the treatment of COPD.

scholarly journals Hydrogen sulfide alleviates cigarette smoke-induced COPD through inhibition of the TGF-β1/smad pathway

2020 ◽  
Vol 245 (3) ◽  
pp. 190-200 ◽  
Author(s):  
Liang Wang ◽  
Jing Meng ◽  
Caicai Wang ◽  
Chao Yang ◽  
Yuan Wang ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Hydrogen Sulfide ◽  
Pulmonary Disease ◽  
Cigarette Smoke ◽  
Airway Remodeling ◽  
Disease Model ◽  
Lung Edema ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Tgf Β1

Smoking has become a major cause of chronic obstructive pulmonary disease through weakening of the respiratory mucus-ciliary transport system, impairing cough reflex sensitivity, and inducing inflammation. Recent researches have indicated that hydrogen sulfide is essential in the development of various lung diseases. However, the effect and mechanism of hydrogen sulfide on cigarette smoke-induced chronic obstructive pulmonary disease have not been reported. In this study, rats were treated with cigarette smoke to create a chronic obstructive pulmonary disease model followed by treatment with a low concentration of hydrogen sulfide. Pulmonary function, histopathological appearance, lung edema, permeability, airway remodeling indicators, oxidative products/antioxidases levels, inflammatory factors in lung, cell classification in bronchoalveolar lavage fluid were measured to examine the effect of hydrogen sulfide on chronic obstructive pulmonary disease model. The results showed that hydrogen sulfide effectively improved pulmonary function and reduced histopathological changes, lung edema, and permeability. Airway remodeling, oxidative stress, and inflammation were also reduced by hydrogen sulfide treatment. To understand the mechanisms, we measured the expression of TGF-β1, TGF-βIand TGF-βII receptors and Smad7 and phosphorylation of Smad2/Smad3. The results indicated that the TGF-β1 and Smad were activated in cigarette smoke-induced chronic obstructive pulmonary disease model, but inhibited by hydrogen sulfide. In conclusion, this study showed that hydrogen sulfide treatment alleviated cigarette smoke-induced chronic obstructive pulmonary disease through inhibition of the TGF-β1/Smad pathway. Impact statement COPD has become a severe public health issue in the world and smoking has become a major cause of COPD. As a result, it is a demandingly needed to explore new potential therapy for cigarette smoke-associated COPD. The present study suggested that H2S treatment improved pulmonary function and reduced histopathological changes, lung edema, permeability, inflammation, airway remodeling and oxidative injury in a COPD model induced by cigarette smoke. Although additional studies are required to elucidate the pharmacodynamics, pharmacokinetics, and pharmacology of H2S in the cigarette smoke-associated COPD, our findings provide an experimental basis for the potential clinical application of H2S in COPD treatment.

scholarly journals Eosinophilic Airway Inflammation in Patients with Stable Biomass Smoke- versus Tobacco Smoke-Associated Chronic Obstructive Pulmonary Disease

2019 ◽  
Vol 9 (24) ◽  
Author(s):  
Lalita Fernandes ◽  
Shraddha Rane ◽  
Suresh Mandrekar ◽  
Anthony Menezes Mesquita
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Tobacco Smoke ◽  
Induced Sputum ◽  
Biomass Fuel ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Biomass Smoke ◽  
Severity Of Disease ◽  
Inflammatory Profile

Background. Chronic obstructive pulmonary disease (COPD) is an inflammatory disease with predominant involvement of neutrophils, macrophages and CD8+ lymphocytes. Eosinophilic airway inflammations are reported in stable state and during acute exacerbations of tobacco smoke-associated COPD (TS-COPD). Women exposed to biomass fuel smoke are known to have eosinophils in sputum. However, little is known about the sputum cellular inflammatory profile in biomass fuel smoke-associated COPD (BMS-COPD). We therefore aimed to compare the sputum cellular inflammatory profile in tobacco smoke- and biomass smoke-associated COPD. Methods. The study was conducted in a tertiary care hospital in Goa, India. A total of 113 patients with stable COPD reporting to the outpatient pulmonary clinic were recruited. All participants were ≥ 40 years of age. Sputum induction studies were performed by the method of Pizzichini et al. after baseline subject characterization. Significant eosinophilia was defined as induced sputum eosinophils ≥ 3%. Results. There were 85 TS-COPD and 28 BMS-COPD patients. The mean age [standard deviation (SD)] was 64.7 (7.8) and 63.0 years (8.3), p = 0.32 in TS and BMS-COPD, respectively. Eighteen subjects (21.1%) were female smokers. The smoking pack-year median [interquartile range (IQR)] was 36 (20, 58) and hour-years of biomass smoke exposure mean (SD) was 192.4 (61). The TS-COPD and BMS-COPD cases showed a post-bronchodilator forced expiratory volume in one second (FEV1%) mean (SD) of 57.9 (17.1), and 62.6 (19.4), p= 0.22, respectively. Both groups had similar symptoms and severity of disease. Induced sputum total cell count per gram of sputum × 106 mean (SD) was 3.05 (1.53) for TS-COPD, and 2.55(1.37) for BMS-COPD p=0.12. The neutrophils % mean (SD) was 86.4 (16.5) and 87.9 (10.2), p = 0.64; eosinophils % median (IQR) was 2.5 (1, 10) and 8 (2, 12.8), p = 0.07; lymphocytes % median (IQR) was 0 (0, 0.75) and 0 (0, 1) p = 0.13; macrophages % median (IQR) was 2.5 (0.75, 5.7) and 1 (0, 4.7) p = 0.13; and significant eosinophilia (eosinophils ≥3%) was 42 (49.4%) and 20 (71%), p=0.04, for TS-COPD and BMS-COPD, respectively. Conclusions. For similar severity of disease and clinical symptoms, significant eosinophilic inflammation was observed in stable BMS-COPD, while both groups had similar neutrophilic inflammation. Participant Consent. Obtained. Ethics Approval. The study was approved by the Institutional Ethics Committee of the Goa Medical College, Goa, India. Competing Interests. The authors declare no competing financial interests.

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