Similar gene expression profiles in smokers and patients with moderate COPD

Llinàs, Laia; Peinado, Víctor I.; Goñi, JoséM.; Rabinovich, Roberto; Pizarro, Sandra Martínez; Rodríguez-Roisín, Robert; Barberà, Joan Albert; Bastos, Ricardo

doi:10.1016/j.pupt.2010.10.010

Cited by 47 publications

(43 citation statements)

References 48 publications

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“…In a study by Churg et al (28), it was shown that, in contrast to control mice, MMP-12-deficient mice did not exhibit an increase in whole lung TNF-␣ levels following cigarette smoke exposure, indicating that MMP-12 may correlate to a TNF-␣-induced inflammatory response. Elevated levels of MMP-1, MMP-2, and MMP-9 have been observed in the lung tissue of COPD subjects (58,74). Moreover, researchers have found that inhalation of cigarette smoke has an equal effect on the concentration of MMP-1 in both COPD patients and healthy individuals (28,116).…”

Section: Effects Of Tobacco On the Immune System In Copdmentioning

confidence: 99%

Interrelated role of cigarette smoking, oxidative stress, and immune response in COPD and corresponding treatments

Zuo

Sergakis

et al. 2014

American Journal of Physiology-Lung Cellular and Molecular Phys

216

139

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Cigarette smoking (CS) can impact the immune system and induce pulmonary disorders such as chronic obstructive pulmonary disease (COPD), which is currently the fourth leading cause of chronic morbidity and mortality worldwide. Accordingly, the most significant risk factor associated with COPD is exposure to cigarette smoke. The purpose of the present study is to provide an updated overview of the literature regarding the effect of CS on the immune system and lungs, the mechanism of CS-induced COPD and oxidative stress, as well as the available and potential treatment options for CS-induced COPD. An extensive literature search was conducted on the PubMed/Medline databases to review current COPD treatment research, available in the English language, dating from 1976 to 2014. Studies have investigated the mechanism by which CS elicits detrimental effects on the immune system and pulmonary function through the use of human and animal subjects. A strong relationship among continued tobacco use, oxidative stress, and exacerbation of COPD symptoms is frequently observed in COPD subjects. In addition, therapeutic approaches emphasizing smoking cessation have been developed, incorporating counseling and nicotine replacement therapy. However, the inability to reverse COPD progression establishes the need for improved preventative and therapeutic strategies, such as a combination of intensive smoking cessation treatment and pharmaceutical therapy, focusing on immune homeostasis and redox balance. CS initiates a complex interplay between oxidative stress and the immune response in COPD. Therefore, multiple approaches such as smoking cessation, counseling, and pharmaceutical therapies targeting inflammation and oxidative stress are recommended for COPD treatment.

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Section: Effects Of Tobacco On the Immune System In Copdmentioning

confidence: 99%

Interrelated role of cigarette smoking, oxidative stress, and immune response in COPD and corresponding treatments

Zuo

Sergakis

et al. 2014

American Journal of Physiology-Lung Cellular and Molecular Phys

216

139

View full text Add to dashboard Cite

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“…Increased whole lung MMP-1 mRNA and protein has been demonstrated in human and guinea pig emphysema [48,76,77], with increased immunoreactivity found in macrophages and in airway epithelium. GOSSELINK et al [51] reported that MMP-1 gene expression increases in the parenchyma from GOLD stage 0 to 3/4, although the magnitude of the difference overall was fairly small.…”

Section: Emphysema: Role Of Other Mmpsmentioning

confidence: 99%

“…PCR analysis on bulk lung samples has shown upregulation of MMP-9 in smokers with severe COPD, with negative correlations with FEV1, diffusing capacity of the lung for carbon monoxide and arterial oxygen tension, and positive correlations with arterial carbon dioxide tension [76]. GOSSELINK et al [51], using laser capture microdissection, found upregulation of gene expression for MMP-9 in the parenchyma that correlated with the progression of GOLD categories of COPD.…”

Section: Series: Mmps In Lung Health and Diseasementioning

confidence: 99%

Matrix metalloproteinases in COPD

Churg

Zhou²,

Wright³

2011

Eur Respir J

240

116

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There is considerable evidence that matrix metalloproteinases (MMPs) are up-and/or downregulated in chronic obstructive pulmonary disease (COPD), particularly in emphysema, in which they probably participate in proteolytic attack on the alveolar wall matrix. Recent data suggest that MMPs also have major roles in driving inflammation or shutting it down, as well as modifying the release of fibrogenic growth factors, processes that are important in the genesis of the various lesions of COPD. In cigarette smoke-induced animal models of emphysema, MMP-12 appears to play a consistent and important role, whereas the data for other MMPs are difficult to interpret. In human lungs, evidence for a role for MMPs is more tenuous and there are numerous contradictions in the literature. Little is known about the effects of MMPs in small airway remodelling, smokeinduced pulmonary hypertension and chronic bronchitis, but MMP-12 participates in experimental small airway modelling. To date, the accumulated data suggest that selective inhibition of MMP-12 might be a viable therapy for emphysema and small airway remodelling, but subtle differences in the functions of MMP-12 in animals and humans mandate caution with this approach. Whether inhibition of other MMPs might be useful is unclear.

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“…Hence, increased levels of both IL-18 and IL-12 [19,53] in lungs exposed to cigarette smoke may induce pulmonary MMP-9 production that could participate in the development of emphysema. Smokers with severe COPD have increased MMP-9 mRNA in pulmonary tissue, and MMP-9 correlates negatively with FEV 1 , diffusion capacity of carbon monoxide, and the partial pressure of oxygen, indicating that MMP-9 is related to the severity of COPD [54]. The link between MMP-9 and emphysema was strengthened by a study showing that mice overexpressing human MMP-9 develop emphysema [42].…”

Section: Pulmonary Gene Expression Of Interferon (Inf)-γ (A) Intermentioning

confidence: 99%

IL-18 and IL-12 synergy induces matrix degrading enzymes in the lung

Cero¹,

Hillestad²,

Løberg³

et al. 2012

Experimental Lung Research

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Interleukin (IL)-18 is a pro-inflammatory cytokine suggested to be involved in the development of pulmonary emphysema and inflammation. Studies involving immunology and cancer have revealed that IL-18 can have synergistic effects with IL-12. We have studied the presence of IL-18 and IL-12 receptors (IL-18R/IL-12R) in the lungs and whether IL-18 and IL-12, alone or in combination, have the ability to initiate the induction of mediators related to the development of emphysema and inflammation. The expression of the IL-18R was abundant in lungs compared to other organs (heart, liver, and spleen), and the IL-12R was also expressed in lung tissue. Mice treated with i.p. injection of recombinant murine IL-18 or IL-12 expressed significantly higher pulmonary mRNA levels of the matrix degrading enzymes metalloproteinase (MMP) 12 and cathepsin S, in addition to interferon-γ, tumor necrosis factor-α, and CXC chemokine ligand 9 (CXCL9) (all P < .05) than controls (received PBS). Treatment with IL-18 and IL-12 in combination showed an even more pronounced induction of these mediators, as well as a significant increase in MMP-9, IL-6, IL-1β, and transforming growth factor-β (P < .05). Furthermore, cellular apoptosis in lung tissue was induced. Immunohistochemical analysis revealed T-cell infiltration in pulmonary vessels following co-stimulation. In summary, IL-18 and IL-12 exert a synergistic effect on the lungs by inducing MMPs, cathepsins S, and pro-inflammatory cytokines, which may promote pulmonary emphysema and inflammation. The synergy between IL-18 and IL-12 involves infiltration of T-cells in the lungs, possibly induced by the T-cell chemoattractant CXCL9.

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Similar gene expression profiles in smokers and patients with moderate COPD

Cited by 47 publications

References 48 publications

Interrelated role of cigarette smoking, oxidative stress, and immune response in COPD and corresponding treatments

Interrelated role of cigarette smoking, oxidative stress, and immune response in COPD and corresponding treatments

Matrix metalloproteinases in COPD

IL-18 and IL-12 synergy induces matrix degrading enzymes in the lung

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