Microsatellite DNA Instability in COPD

Siafakas, Nikolaos M.; Tzortzaki, Eleni G.; Sourvinos, George; Bouros, Demosthenes; Tzanakis, Νikolaos; Kafatos, Antony; Spandidos, Demetrios Α.

doi:10.1378/chest.116.1.47

Cited by 75 publications

(80 citation statements)

References 18 publications

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“…The inflammation in COPD patients is thought to become chronic because of the vicious cycle between inflammation and DNA damage that occurs as a result of this positive feedback. In contrast to ''susceptible'' smokers, healthy smokers do not develop DNA damage [32][33][34][35]38], presumably because of a lower severity of inflammatory cell infiltration resulting in the production of smaller amounts of ROS or RNS, more efficient adaptation by antioxidant induction, and/or more efficient DNA repair mechanisms. Based on this hypothesis, we propose that DNA damage in a smoker is the determining event in the progression to COPD.…”

Section: Dna Damage and Sasp As A Persistent Source Of Inflammatory Mmentioning

confidence: 94%

“…In COPD, DNA damage may arise from the ROS or RNS released by inflammatory cells as well as the ROS present in tobacco smoke [31]. In fact, accumulating evidence suggests the occurrence of DNA damage in COPD [32][33][34][35][36][37][38][39][40][41][42].…”

Section: Induction Of Chronic Inflammation By Dna Damagementioning

confidence: 99%

“…Many investigators, including our own group, have reported the occurrence of DNA damage (including DNA oxidation and methylation, microsatellite DNA instability, loss of heterozygosity, and DNA doublestrand breaks) in the lung tissue of COPD patients [32][33][34][35][36][37][38]. DNA breaks have also been observed in peripheral blood lymphocytes [40,43].…”

Section: Dna Damage and Sasp As A Persistent Source Of Inflammatory Mmentioning

confidence: 99%

“…First, the actual occurrence of DNA damage during an early stage of COPD will need to be confirmed. DNA damage has already been reported to occur in the lung tissue of COPD patients, but many of the reported results were obtained in studies that compared control smokers with patients who had moderate-to-severe COPD [32][33][34][35][36]38]. If the occurrence of DNA damage is the determining event that separates healthy smokers from COPD patients, DNA damage should have occurred even in patients with mild COPD and should progress as the severity of COPD increases.…”

Section: Dna Damage and Sasp As A Persistent Source Of Inflammatory Mmentioning

confidence: 99%

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The danger signal plus DNA damage two-hit hypothesis for chronic inflammation in COPD

et al. 2013

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Inflammation in chronic obstructive pulmonary disease (COPD) is thought to originate from the activation of innate immunity by a danger signal (first hit), although this mechanism does not readily explain why the inflammation becomes chronic. Here, we propose a two-hit hypothesis explaining why inflammation becomes chronic in patients with COPD. A more severe degree of inflammation exists in the lungs of patients who develop COPD than in the lungs of healthy smokers, and the large amounts of reactive oxygen species and reactive nitrogen species released from inflammatory cells are likely to induce DNA double-strand breaks (second hit) in the airways and pulmonary alveolar cells, causing apoptosis and cell senescence. The DNA damage response and senescence-associated secretory phenotype (SASP) are also likely to be activated, resulting in the production of pro-inflammatory cytokines. These pro-inflammatory cytokines further stimulate inflammatory cell infiltration, intensifying cell senescence and SASP through a positive-feedback mechanism. This vicious cycle, characterised by mutually reinforcing inflammation and DNA damage, may cause the inflammation in COPD patients to become chronic. Our hypothesis helps explain why COPD tends to occur in the elderly, why the inflammation worsens progressively, why inflammation continues even after smoking cessation, and why COPD is associated with lung cancer. @ERSpublications A vicious cycle, involving mutually reinforcing inflammation and DNA damage, may cause chronic inflammation in COPD http://ow.ly/nYW4u

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Section: Dna Damage and Sasp As A Persistent Source Of Inflammatory Mmentioning

confidence: 94%

Section: Induction Of Chronic Inflammation By Dna Damagementioning

confidence: 99%

Section: Dna Damage and Sasp As A Persistent Source Of Inflammatory Mmentioning

confidence: 99%

Section: Dna Damage and Sasp As A Persistent Source Of Inflammatory Mmentioning

confidence: 99%

See 2 more Smart Citations

The danger signal plus DNA damage two-hit hypothesis for chronic inflammation in COPD

et al. 2013

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“…[26,27] It was reported in 1999 that MSI was found exclusively in the sputum cells of smokers with COPD, which indicated that genetic alteration might increase susceptibility to COPD. [28] Another study revealed that MSI was found in 38% COPD patients (14 out of 36), while none was found in bronchiectasis or control subjects (non-COPD smokers, healthy subjects). [29] Loss of heterozygosity (LOH) was also observed in epithelial barrier cells of COPD patients.…”

Section: Dna Dsbsmentioning

confidence: 99%