Latent adenoviral infection induces production of growth factors relevant to airway remodeling in COPD

Ogawa, Emiko; Elliott, W. Mark; Hughes, Fiona; Eichholtz, Thomas; Hogg, James C.; Hayashi, Shizu

doi:10.1152/ajplung.00315.2002

Cited by 34 publications

(22 citation statements)

References 56 publications

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“…The resulting clones that express E1A but not E1B are referred to as HA35-1 and HA57, respectively. Similar levels of E1A protein expression in these two cell lines have been reported (35). One cell line from the same patient from which HA35-1 was developed was transfected with this plasmid DNA but did not express E1A mRNA or protein.…”

Section: Methodssupporting

confidence: 76%

Adenovirus E1A regulates lung epithelial ICAM-1 expression by interacting with transcriptional regulators at its promoter

Morimoto¹,

Gosselink²,

Kartono³

et al. 2009

American Journal of Physiology-Lung Cellular and Molecular Phys

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We focused on the regulation of inflammatory mediator expression by adenovirus E1A in lung epithelial cells and the role of this viral protein in the pathogenesis of chronic obstructive pulmonary disease (COPD). We previously reported that E1A, a well-known regulator of host genes, increased ICAM-1 expression in human bronchial epithelial (HBE) and A549 cells in response to LPS stimulation. In this report, we clarified the mechanism of this regulation. We found NF-κB translocation to the nucleus after LPS stimulation in both E1A-positive and -negative HBE cells. ICAM-1 promoter reporter constructs revealed that a mutation in the proximal NF-κB binding site completely inhibited increased transcription, whereas the mutation in a distal site did not. We analyzed the participation of E1A in transcriptional complex formation at this promoter using chromatin immunoprecipitation. In E1A-positive HBE and A549 cells, LPS stimulation increased ICAM-1 promoter immunoprecipitation by NF-κB p65 and p300 but not activator protein-1 antibodies with a concomitant increase by the E1A antibody. No increase was found in E1A-negative cells except in HBE cells with p65 antibody. The association of E1A with the increased promoter immunoprecipitation with p300 was also observed after TNF-α stimulation of A549 cells. These results suggest that adenovirus E1A regulates the ICAM-1 promoter through its proximal NF-κB binding site, most likely by interacting with the transcriptional complex that forms at this site. E1A regulation of the LPS response may play a role in acute exacerbations as a consequence of bacterial infections in COPD.

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Section: Methodssupporting

confidence: 76%

Adenovirus E1A regulates lung epithelial ICAM-1 expression by interacting with transcriptional regulators at its promoter

Morimoto¹,

Gosselink²,

Kartono³

et al. 2009

American Journal of Physiology-Lung Cellular and Molecular Phys

Self Cite

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“…TGFβ1 expression is particularly increased in the epithelium of small airways in COPD [93]. The adenoviral E1A gene induces the release of the growth factors CTGF and TGFβ1 in human bronchial epithelial cells [94]. Growth factors may also stimulate the proliferation and growth of airway smooth muscle cells.…”

Section: Airway Wall Remodelling Mediatorsmentioning

confidence: 99%

Inflammatory Mediators in Chronic Obstructive Pulmonary Disease

Chung¹

2005

CDTIA

153

108

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Chronic obstructive pulmonary disease (COPD) is characterised by chronic obstruction of expiratory flow affecting peripheral airways, associated with chronic bronchitis (mucus hypersecretion with goblet cell and submucosal gland hyperplasia) and emphysema (destruction of airway parenchyma), together with fibrosis and tissue damage, and inflammation of the small airways. Inflammatory mediators include lipid mediators, chemokines, cytokines, growth factors, reactive oxygen species and proteinases. Increased levels of interleukin (IL)-6, IL-1beta, tumour necrosis factor-alpha (TNF-alpha) and IL-8 have been measured in sputum, with further increases during exacerbations, and the bronchiolar epithelium over-expresses MCP-1 and IL-8. IL-8 and LTB4 can account for neutrophil chemotactic activity of sputum. The expression of chemokines such as RANTES and eotaxin may underlie the airway eosinophilia observed in some COPD patients. Reactive oxygen species can increase gene expression of many inflammatory mediators, such as IL-1 and TNFalpha from macrophages, alveolar and bronchial epithelial cells. TNFalpha and IL-1beta stimulate macrophages to produced matrix metalloproteinase-9 (MMP-9), and bronchial epithelial cells to produce extracellular matrix glycoproteins such as tenascin. Increased expression of transforming growth factor-beta (TGFbeta) and of epidermal growth factor (EGF) occurs in the epithelium and submucosal cells of patients with chronic bronchitis. TGFbeta and EGF activate proliferation of fibroblasts, while activation of the EGF receptor leads to mucin gene expression.

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“…Recent evidence suggests that latent adenoviral infection may be associated with the pathogenesis of COPD by a mechanism which involves enhancing lung inflammation [126][127][128]. The link is with the E1A protein derived from latent adenoviral infection which interacts with transcription factors and co-factors so enhancing nuclear binding of transcription factors [126].…”

Section: Adenoviral Infection and Copdmentioning

confidence: 99%

Oxidants and COPD

MacNee¹

2005

CDTIA

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Smoking is the main etiologic factor in chronic obstructive pulmonary disease (COPD). Cigarette smoke produces an enormous oxidant burden on the lungs, which is exacerbated by the release of oxidants from inflammatory cells. There is considerable evidence that an increased oxidative burden occurs in the lungs of patients with COPD, and this may be involved in many of the pathogenic processes, such as direct injury to lung cells, mucus hypersecretion, inactivation of antiproteases, and enhancing lung inflammation through activation of redox-sensitive transcription factors. COPD is also recognized to have multiple systemic consequences, such as weight loss and skeletal muscle dysfunction. Moreover, it is appreciated that oxidative stress extends beyond the lung and may, through similar oxidative stress mechanisms as those in the lung, contribute to several of the systemic manifestations in COPD such as skeletal muscle dysfunction. Thus, there is a great need for an effective antioxidant therapy to modulate the oxidative stress in COPD, since this may be an important therapeutic target.

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Latent adenoviral infection induces production of growth factors relevant to airway remodeling in COPD

Cited by 34 publications

References 56 publications

Adenovirus E1A regulates lung epithelial ICAM-1 expression by interacting with transcriptional regulators at its promoter

Adenovirus E1A regulates lung epithelial ICAM-1 expression by interacting with transcriptional regulators at its promoter

Inflammatory Mediators in Chronic Obstructive Pulmonary Disease

Oxidants and COPD

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