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Probing Cellular and Molecular Mechanisms of Cigarette Smoke-Induced Immune Response in the Progression of Chronic Obstructive Pulmonary Disease Using Multiscale Network Modeling

View Article: PubMed Central - PubMed

ABSTRACT

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disorder characterized by progressive destruction of lung tissues and airway obstruction. COPD is currently the third leading cause of death worldwide and there is no curative treatment available so far. Cigarette smoke (CS) is the major risk factor for COPD. Yet, only a relatively small percentage of smokers develop the disease, showing that disease susceptibility varies significantly among smokers. As smoking cessation can prevent the disease in some smokers, quitting smoking cannot halt the progression of COPD in others. Despite extensive research efforts, cellular and molecular mechanisms of COPD remain elusive. In particular, the disease susceptibility and smoking cessation effects are poorly understood. To address these issues in this work, we develop a multiscale network model that consists of nodes, which represent molecular mediators, immune cells and lung tissues, and edges describing the interactions between the nodes. Our model study identifies several positive feedback loops and network elements playing a determinant role in the CS-induced immune response and COPD progression. The results are in agreement with clinic and laboratory measurements, offering novel insight into the cellular and molecular mechanisms of COPD. The study in this work also provides a rationale for targeted therapy and personalized medicine for the disease in future.

No MeSH data available.


Related in: MedlinePlus

Effects of cigarette smoking cessation on TD dynamics.Smoking cessation occurs after t = 400, 800, 900, 1500, and 2500 days of CS exposure, respectively.
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pone.0163192.g008: Effects of cigarette smoking cessation on TD dynamics.Smoking cessation occurs after t = 400, 800, 900, 1500, and 2500 days of CS exposure, respectively.

Mentions: Cigarette smoking cessation is considered a most important intervention to reduce COPD progression [10]. The dynamics of TD is shown in Fig 8 as cigarette smoking cessation occurs after different days of CS exposure (S = 1.67) with the parameters in Table A in S1 File. Our simulations demonstrate that when early smoking cessation happens before 920 days of CS exposure, TD falls to the baseline and COPD is prevented (Fig 8). Smoking cessation starting after day 920 leads to the reduction of TD to some extent, but COPD and inflammatory responses persist (Figure C in S1 File). Our results are qualitatively consistent with experimental and clinical observations [64–66]. Analysis of positive feedback loops will elucidate further these effects of smoking cessation as discussed later.


Probing Cellular and Molecular Mechanisms of Cigarette Smoke-Induced Immune Response in the Progression of Chronic Obstructive Pulmonary Disease Using Multiscale Network Modeling
Effects of cigarette smoking cessation on TD dynamics.Smoking cessation occurs after t = 400, 800, 900, 1500, and 2500 days of CS exposure, respectively.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5036797&req=5

pone.0163192.g008: Effects of cigarette smoking cessation on TD dynamics.Smoking cessation occurs after t = 400, 800, 900, 1500, and 2500 days of CS exposure, respectively.
Mentions: Cigarette smoking cessation is considered a most important intervention to reduce COPD progression [10]. The dynamics of TD is shown in Fig 8 as cigarette smoking cessation occurs after different days of CS exposure (S = 1.67) with the parameters in Table A in S1 File. Our simulations demonstrate that when early smoking cessation happens before 920 days of CS exposure, TD falls to the baseline and COPD is prevented (Fig 8). Smoking cessation starting after day 920 leads to the reduction of TD to some extent, but COPD and inflammatory responses persist (Figure C in S1 File). Our results are qualitatively consistent with experimental and clinical observations [64–66]. Analysis of positive feedback loops will elucidate further these effects of smoking cessation as discussed later.

View Article: PubMed Central - PubMed

ABSTRACT

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disorder characterized by progressive destruction of lung tissues and airway obstruction. COPD is currently the third leading cause of death worldwide and there is no curative treatment available so far. Cigarette smoke (CS) is the major risk factor for COPD. Yet, only a relatively small percentage of smokers develop the disease, showing that disease susceptibility varies significantly among smokers. As smoking cessation can prevent the disease in some smokers, quitting smoking cannot halt the progression of COPD in others. Despite extensive research efforts, cellular and molecular mechanisms of COPD remain elusive. In particular, the disease susceptibility and smoking cessation effects are poorly understood. To address these issues in this work, we develop a multiscale network model that consists of nodes, which represent molecular mediators, immune cells and lung tissues, and edges describing the interactions between the nodes. Our model study identifies several positive feedback loops and network elements playing a determinant role in the CS-induced immune response and COPD progression. The results are in agreement with clinic and laboratory measurements, offering novel insight into the cellular and molecular mechanisms of COPD. The study in this work also provides a rationale for targeted therapy and personalized medicine for the disease in future.

No MeSH data available.


Related in: MedlinePlus