Inflammation and remodeling in chronic obstructive pulmonary disease

Hamid, Qutayba; Cosio, Manuel G.; Lim, Sam

doi:10.1016/j.jaci.2004.10.016

Cited by 14 publications

(14 citation statements)

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“…This pathology is also associated with an airway inflammation process characterized by intense accumulation of inflammatory cells, such as macrophages and neutrophils, in airways and lung 3,4. It is believed that the development of emphysema, which is the most important histological finding of COPD, reflects a relative excess of proteases that degrade the connective tissues of the lung and a relative paucity of anti-proteolytic defenses 26.…”

Section: Discussionmentioning

confidence: 99%

“…Histological observations of both biopsy specimens of patients with COPD show structural abnormalities such as increased smooth muscle mass; subepithelial fibrosis; and thickening of airway walls, with the intense infiltration of inflammatory cells, including macrophages and neutrophils 3,4. These cellular events are now called tissue remodeling and involve extensive alteration of extracellular matrix (ECM), which is essential for supporting normal lung functions 5…”

Section: Introductionmentioning

confidence: 99%

“…There is much evidence showing that administration of TBH in COPD patients could prevent airway smooth muscle remodeling 21,22. Although these reports may suggest that TBH exerts a suppressive effect on MMP production, or inhibition of MMP activation in airways, there is little evidence showing the influence of TBH on MMPs 12.…”

Section: Introductionmentioning

confidence: 99%

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Tiotropium bromide inhibits TGF-ß-induced MMP production from lung fibroblasts by interfering with Smad and MAPK pathways in vitro

Asano

Shikama²,

Shoji³

et al. 2010

COPD

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Background:Chronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation and structural alterations (ie, tissue remodeling) throughout the conducting airways, parenchyma, and pulmonary vasculature. Matrix metalloproteinases (MMPs) are extracellular degrading enzymes that play a critical role in inflammatory cell infiltration and tissue remodeling, but the influence of the agents that are used for the treatment of COPD on the production of MMPs is not well understood.Purpose:The present study aimed to examine the influence of tiotropium bromide hydrate (TBH) on the production of MMPs from lung fibroblasts (LFs) induced by transforming growth factor (TGF)-β in vitro.Methods:LFs, at a concentration of 5 × 105 cells·mL−1, were stimulated with TGF-β in the presence of various concentrations of TBH. MMP-1 and MMP-2 levels in culture supernatants were examined by enzyme-linked immunosorbent assay (ELISA), and MMP messenger ribonucleic acid (mRNA) expression was examined by real-time polymerase chain reaction (RT-PCR). The influence of TBH on TGF-β signaling pathways was also analyzed by examining Smad activation and signaling protein phosphorylation by ELISA.Results:TBH at more than 15 pg·mL−1 inhibited the production of MMP-1 and MMP-2, but not tissue inhibitor of matrix metalloproteinase (TIMP)-1 and TIMP-2, from LFs, after TGF-β stimulation. TBH also suppressed MMP mRNA expression through the inhibition of Smad activation and signaling protein, extracellular-signal-regulated kinase (ERK) 1 and 2, and c-Jun N-terminal kinase (JNK), phosphorylation.Conclusion:These results may suggest that TBH suppresses MMP production from LFs, through interference of TGF-β-mediated signaling pathways and results in favorable modification of the clinical status of COPD.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Tiotropium bromide inhibits TGF-ß-induced MMP production from lung fibroblasts by interfering with Smad and MAPK pathways in vitro

Asano

Shikama²,

Shoji³

et al. 2010

COPD

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“…CD8 + T cells are regarded as a hallmark cell of COPD, and are increased in both the central [6] and peripheral [7] airways of COPD patients. CD8 + T cells found within the airways are generally located within the submucosa and invading the epithelium [8,9]. Unfortunately, the role of CD8 + T cells in COPD and the mechanisms by which they are recruited to the lung are still generally unknown.…”

Section: Introductionmentioning

confidence: 99%

Cigarette smoke increases TLR4 and TLR9 expression and induces cytokine production from CD8+T cells in chronic obstructive pulmonary disease

et al. 2011

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BackgroundCigarette smoke is a major risk factor for chronic obstructive pulmonary disease (COPD), an inflammatory lung disorder. COPD is characterized by an increase in CD8+ T cells within the central and peripheral airways. We hypothesized that the CD8+ T cells in COPD patients have increased Toll-like receptor (TLR) expression compared to control subjects due to the exposure of cigarette smoke in the airways.MethodsEndobronchial biopsies and peripheral blood were obtained from COPD patients and control subjects. TLR4 and TLR9 expression was assessed by immunostaining of lung tissue and flow cytometry of the peripheral blood. CD8+ T cells isolated from peripheral blood were treated with or without cigarette smoke condensate (CSC) as well as TLR4 and TLR9 inhibitors. PCR and western blotting were used to determine TLR4 and TLR9 expression, while cytokine secretion from these cells was detected using electrochemiluminescence technology.ResultsNo difference was observed in the overall expression of TLR4 and TLR9 in the lung tissue and peripheral blood of COPD patients compared to control subjects. However, COPD patients had increased TLR4 and TLR9 expression on lung CD8+ T cells. Exposure of CD8+ T cells to CSC resulted in an increase of TLR4 and TLR9 protein expression. CSC exposure also caused the activation of CD8+ T cells, resulting in the production of IL-1β, IL-6, IL-10, IL-12p70, TNFα and IFNγ. Furthermore, inhibition of TLR4 or TLR9 significantly attenuated the production of TNFα and IL-10.ConclusionsOur results demonstrate increased expression of TLR4 and TLR9 on lung CD8+ T cells in COPD. CD8+ T cells exposed to CSC increased TLR4 and TLR9 levels and increased cytokine production. These results provide a new perspective on the role of CD8+ T cells in COPD.

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“…In COPD, remodeling changes are particularly prominent in the small airways (Ͻ2 mm in internal diameter), which are not easily accessible, and most of the information has been available from resection specimens from smokers undergoing lung surgery for tumors or from postmortem specimens. The remodeling changes are also described in the large airways (4). This article examines the components of airway wall remodeling in COPD, their relationship to airflow limitation, the effects of some current treatments, and the potential contribution of airway smooth muscle and matrix changes.…”

mentioning

confidence: 99%

The Role of Airway Smooth Muscle in the Pathogenesis of Airway Wall Remodeling in Chronic Obstructive Pulmonary Disease

Chung¹

2005

Proceedings of the American Thoracic Society

105

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Airway wall remodeling processes are present in the small airways of patients with chronic obstructive pulmonary disease, consisting of tissue repair and epithelial metaplasia that contribute to airway wall thickening and airflow obstruction. With increasing disease severity, there is also increased mucous metaplasia and submucosal gland hypertrophy, peribronchial fibrosis, and an increase in airway smooth muscle mass. Apart from its contractile properties, airway smooth muscle produces inflammatory cytokines, proteases, and growth factors, which may contribute to the remodeling process and induce phenotypic changes of the muscle. Airflow limitation responds minimally to ␤-agonists and corticosteroid therapy, unlike asthma, perhaps because of alterations in ␤-receptor or glucocorticoid receptor numbers, alterations in receptor signaling, or the constrictive limitation imposed by peribronchial fibrosis. Better response is observed with the combination of inhaled long-acting ␤-agonists and corticosteroids. This could result from effects at the level of airway smooth muscle. Airway wall remodeling may involve the release of growth factors from inflammatory or resident cells. The influence of smoking cessation or of current therapies on airway wall remodeling is unknown. Specific therapies for airway wall remodeling may be necessary, together with noninvasive methods of imaging small airway wall remodeling to assess responses.

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Inflammation and remodeling in chronic obstructive pulmonary disease

Cited by 14 publications

References 4 publications

Tiotropium bromide inhibits TGF-ß-induced MMP production from lung fibroblasts by interfering with Smad and MAPK pathways in vitro

Tiotropium bromide inhibits TGF-ß-induced MMP production from lung fibroblasts by interfering with Smad and MAPK pathways in vitro

Cigarette smoke increases TLR4 and TLR9 expression and induces cytokine production from CD8+T cells in chronic obstructive pulmonary disease

The Role of Airway Smooth Muscle in the Pathogenesis of Airway Wall Remodeling in Chronic Obstructive Pulmonary Disease

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Inflammation and remodeling in chronic obstructive pulmonary disease

Cited by 14 publications

References 4 publications

Tiotropium bromide inhibits TGF-&szlig;-induced MMP production from lung fibroblasts by interfering with Smad and MAPK pathways in vitro

Tiotropium bromide inhibits TGF-&szlig;-induced MMP production from lung fibroblasts by interfering with Smad and MAPK pathways in vitro

Cigarette smoke increases TLR4 and TLR9 expression and induces cytokine production from CD8+T cells in chronic obstructive pulmonary disease

The Role of Airway Smooth Muscle in the Pathogenesis of Airway Wall Remodeling in Chronic Obstructive Pulmonary Disease

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Tiotropium bromide inhibits TGF-ß-induced MMP production from lung fibroblasts by interfering with Smad and MAPK pathways in vitro

Tiotropium bromide inhibits TGF-ß-induced MMP production from lung fibroblasts by interfering with Smad and MAPK pathways in vitro