Tumor Necrosis Factor-α Drives 70% of Cigarette Smoke–induced Emphysema in the Mouse

Churg, Andrew; Wang, Rong D.; Tai, Hsin Hsiung; Wang, Xiaoshan; Xie, Changshi; Wright, Joanne L.

doi:10.1164/rccm.200404-511oc

Cited by 314 publications

(245 citation statements)

References 35 publications

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“…TNF-a is a leading cytokine linked to CS-induced emphysema [34]. Indeed, TNFa receptor-knockout mice did not develop an inflammatory infiltrate or matrix breakdown after a single acute CS exposure [35]. In our study, GC-treated mice had down-regulated TNFa mRNA expression and exhibited less infiltration of inflammatory cells and emphysematous changes of airspace in response to CS than did non-treated mice.…”

Section: Discussionsupporting

confidence: 43%

Galla Chinensis Attenuates Cigarette Smoke‐associated Lung Injury by Inhibiting Recruitment of Inflammatory Cells into the Lung

Lee

Lim

et al. 2014

Basic Clin Pharma Tox

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Inflammation is a common feature in the pathogenesis of cigarette smoke (CS)-associated diseases. In this study, we investigated the effects of Galla Chinensis (GC) extract on pulmonary inflammatory responses in a CS-exposed mouse model. In vitro studies showed that GC extract reduced MCP-1 production in a dose-dependent manner. In addition, the recruitment of inflammatory cells into the lung was significantly inhibited in the bronchoalveolar lavage fluid (BALF) of the GC-treated mice after 3 weeks of daily CS exposure. GC treatment down-regulated TNF-a, IL-6 and MCP-1 mRNA expression levels in lung tissue. Finally, GC-treated mice showed less emphysematous change of alveolar compared to mice only exposed to CS. Our results show that GC extract reduces lung inflammation and emphysematous change by inhibiting the infiltration of inflammatory cells to the lung. These data indicate that GC extract is a therapeutic candidate for CS-induced lung injury.

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Section: Discussionsupporting

confidence: 43%

Galla Chinensis Attenuates Cigarette Smoke‐associated Lung Injury by Inhibiting Recruitment of Inflammatory Cells into the Lung

Lee

Lim

et al. 2014

Basic Clin Pharma Tox

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“…TNF-α is also believed to play a central role in the pathophysiology of COPD [60]. It is produced by alveolar macrophages, neutrophils, T cells, mast cells and epithelial cells following contact with different pollutants including cigarette smoke [61].…”

Section: Role Of Tnf-α In Asthma and Copdmentioning

confidence: 99%

TNF-α inhibitors in asthma and COPD: We must not throw the baby out with the bath water

Matera

Calzetta

Cazzola

2010

Pulmonary Pharmacology & Therapeutics

119

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Tumor necrosis factor (TNF)-α, a pleiotropic cytokine that exerts a variety of effects, such as growth promotion, growth inhibition, angiogenesis, cytotoxicity, inflammation, and immunomodulation, has been implicated in several inflammatory conditions. It plays a significant role in many inflammatory diseases of lung. Given that there is significant literature supporting the pathobiologic role of TNF-α in asthma, mainly in severe refractory asthma, and COPD, TNF-α inhibitors (infliximab, golimumab and etanercept) are now regarded as potential new medications in asthma and COPD management. The studies reported in literature indicate that TNF-α inhibitors are effective in a relatively small subgroup of patients with severe asthma, possibly defined by an increased TNF axis, but they seem to be ineffective in COPD, although an observational study demonstrated that TNF-α inhibitors were associated with a reduction in the rate of COPD hospitalisation among patients with COPD receiving these agents to treat their rheumatoid arthritis. These findings require a smart approach because there is still good reason to target TNF-α, perhaps in a more carefully selected patient group. TNF-α treatment should therefore not be thrown out, or abandoned. Indeed, since severe asthma and COPD are heterogeneous diseases that have characteristics that occur with different phenotypes remained poorly characterized and little known about the underlying pathobiology contributing to them, it is likely that definition of these phenotypes and choice of the right outcome measure will allow us to understand which kind of patients can benefit from TNF-α inhibitors.

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“…Overexpression of TNF-α in the lungs of mice results in the development of classic pathologic features of emphysema (Fujita et al 2001). Studies performed in TNF-receptor knockout mice using a cigarette smoke-induced model of emphysema generated a lesser degree of lung disease compared to wild-type animals (Churg et al 2004). However, TNF blockade with Infl iximab, an anti-TNF antibody, did not result in apparent benefi t, with respect to lung function, in patients with moderate to severe COPD, although additional evaluation may be necessary to evaluate whether selected subpopulations (eg, those with cachexia) could specifi cally benefi t (Rennard et al 2007).…”

Section: Tumor Necrosis Factor-alpha (Tnf-α)mentioning

confidence: 99%

Role of T-lymphocytes and pro-inflammatory mediators in the pathogenesis of chronic obstructive pulmonary disease

Gadgil

Duncan

2008

COPD

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Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death in the US and a major worldwide healthcare problem. The pathophysiologic mechanisms that drive development and progression of this disease are complex and only poorly understood. While tobacco smoking is the primary risk factor, other disease processes also appear to play a role. Components of the innate immune system (eg, macrophages and neutrophils) have long been believed to be important in the development of COPD. More recent evidence also suggests involvement of the adaptive immune system in pathogenesis of this disease. Here we will review the literature supporting the participation of T-cells in the development of COPD, and comment on the potential antigenic stimuli that may account for these responses. We will further explore the prospective contributions of T-cell derived mediators that could contribute to the infl ammation, alveolar wall destruction, and small airway fi brosis of advanced COPD. A better understanding of these complex immune processes will lead to new insights that could result in improved preventative and/or treatment strategies.

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Tumor Necrosis Factor-α Drives 70% of Cigarette Smoke–induced Emphysema in the Mouse

Cited by 314 publications

References 35 publications

Galla Chinensis Attenuates Cigarette Smoke‐associated Lung Injury by Inhibiting Recruitment of Inflammatory Cells into the Lung

Galla Chinensis Attenuates Cigarette Smoke‐associated Lung Injury by Inhibiting Recruitment of Inflammatory Cells into the Lung

TNF-α inhibitors in asthma and COPD: We must not throw the baby out with the bath water

Role of T-lymphocytes and pro-inflammatory mediators in the pathogenesis of chronic obstructive pulmonary disease

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