Clusterin Decreases Oxidative Stress in Lung Fibroblasts Exposed to Cigarette Smoke

Carnevali, S; Luppi, Fabrizio; D’Arca, Domenico; Caporali, Andrea; Ruggieri, Maria Paola; Vettori, Maria Vittoria; Caglieri, Andrea; Astancolle, Serenella; Panico, Francesca; Davalli, Pierpaola; Mutti, Antonio; Fabbri, Leonardo M.; Corti, Angelo

doi:10.1164/rccm.200512-1835oc

Cited by 41 publications

(28 citation statements)

References 36 publications

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“…It has previously been reported that cigarette smoke induces oxidative stress in human lung fibroblasts, which may then initiate a process of repair and collagen deposition [41]. Furthermore, the interaction between fibroblasts and inflammatory cells may also play a role in fibrotic remodeling.…”

Section: Structure Of the Small Airways In Established Copdmentioning

confidence: 99%

Pathophysiology of the Small Airways in Chronic Obstructive Pulmonary Disease

Baraldo

Turato

Saetta³

2012

Respiration

104

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Chronic obstructive pulmonary disease (COPD) is characterized by a persistent airflow limitation that is usually progressive and associated with an enhanced chronic inflammatory response in the airways and the lung to noxious particles or gases. From a pathological point of view, COPD is characterized by two distinct and frequently coexisting aspects: small airway abnormalities and parenchymal destruction (or emphysema). When pathological changes are localized in lung parenchyma, they will contribute to airflow limitation by reducing the elastic recoil of the lung through parenchymal destruction, as well as by reducing the elastic load applied to the airways through destruction of alveolar attachments. Conversely, when pathological changes involve the small airways, they will contribute to airflow limitation by narrowing and obliterating the lumen and by actively constricting the airways, therefore increasing the resistance. In this article we will review the structural abnormalities in small airways and their relationship with the disordered pulmonary function in COPD, in the attempt to disentangle the mechanisms contributing to the development and progression of airflow limitation in smokers. We will start by describing the normal structure of the small airways, and then observe the main pathological alterations that accumulate in this site and how they parallel pulmonary function derangement.

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Section: Structure Of the Small Airways In Established Copdmentioning

confidence: 99%

Pathophysiology of the Small Airways in Chronic Obstructive Pulmonary Disease

Baraldo

Turato

Saetta³

2012

Respiration

104

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“…To further analyze the role of the AhR in inflammation, we exposed primary lung fibroblasts from AhR Ϫ/Ϫ as well as from AhR ϩ/Ϫ and AhR ϩ/ϩ mice to increasing concentrations of CSE for 24 h and measured PG production by enzyme immunoassay. The use of CSE for in vitro assessment of tobacco smoke exposure is well described (9,18,44,51,52). Basal levels of immunoregulatory and proinflammatory PGs, namely PGE 2 ( Fig.…”

Section: Characterization Of Ahr Protein Expression and Function In Ahrmentioning

confidence: 99%

The Aryl Hydrocarbon Receptor Attenuates Tobacco Smoke-induced Cyclooxygenase-2 and Prostaglandin Production in Lung Fibroblasts through Regulation of the NF-κB Family Member RelB

Baglole

Maggirwar

Gasiewicz

et al. 2008

Journal of Biological Chemistry

134

178

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Diseases such as chronic obstructive pulmonary disease and lung cancer caused by cigarette smoke affect millions of people worldwide. The aryl hydrocarbon receptor (AhR) is a ligandactivated transcription factor that influences responses to certain environmental pollutants such as tobacco smoke. However, the physiological function(s) of the AhR is unknown. Herein we propose that the physiologic role of the AhR is to limit inflammation. We show that lung fibroblasts from AhR ؊/؊ mice produce a heightened inflammatory response to cigarette smoke, typified by increased levels of cyclooxygenase-2 (COX-2) and prostaglandins (PGs), when compared with wild type (AhR ؉/؉ ) fibroblasts. This response was dependent on AhR expression as transient transfection of an AhR expression plasmid into AhR ؊/؊ fibroblasts significantly attenuated the smoke-induced COX-2 and PG production, confirming the anti-inflammatory role of the AhR. The AhR can interact with NF-B. However, the heightened inflammatory response observed in AhR ؊/؊ fibroblasts was not the result of NF-B (p50/p65) activation. Instead it was coupled with a loss of the NF-B family member RelB in AhR ؊/؊ fibroblasts. Taken together, these studies provide compelling evidence that AhR expression limits proinflammatory COX-2 and PG production by maintaining RelB expression. The association between RelB and AhR may represent a new therapeutic and more selective target with which to combat inflammation-associated diseases.Lung inflammation and diseases such as chronic obstructive pulmonary disease and cancer caused by cigarette smoke affect millions of people. The link between chronic inflammation, typified by heightened expression of cyclooxygenase-2 (COX-2; 2 also known as prostaglandin endoperoxide H synthase (PGHS-2)), and these diseases is well established (1-3). COX enzymes catalyze the transformation of arachidonic acid into prostaglandin (PG) H 2 (4, 5), which serves as a substrate for various synthases that generate PGs and thromboxanes (6). There are two COX isoforms. In most tissues, COX-1 is expressed constitutively (7), whereas COX-2 is rapidly up-regulated by a variety of inflammatory stimuli (5) such as interleukin (IL)-1 (8) and cigarette smoke (9).Cigarette smoke is a complex mixture containing more than 4800 compounds. Cigarette smoke and some of its components, such as benzo[a]pyrene (B[a]P), induce COX-2 expression in lymphocytes, epithelial cells, and fibroblasts (9 -11). Fibroblasts are the main cell type in the lung interstitium, are involved in tissue repair and remodeling (12), provide structural support to the alveolar compartment, and are an important target of cigarette smoke (9, 13-18). Importantly fibroblasts are one of the major cell types that express COX-2 and synthesize PGs in humans (19,20).Regulation of COX-2 expression involves several transcriptional regulators (5), including the aryl hydrocarbon receptor (AhR). The AhR is a ligand-activated transcription factor belonging to the basic helix-loop-helix/Per-Arnt-Sim transcription factor ...

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“…In the multistep process of carcinogenesis, cigarette smoke may act during the initiation and promotion phases of lung carcinogenesis, triggering a cascade of events [3,27]. The target tissue for gases and particles is the tracheo-bronchial epithelium, which acts as a mechanical barrier [10] and is the ideal region for studying the toxicity of inhaled substances [28]. In particular, cigarette smoke can induce cytotoxicity, increased detachment of cells, DNA strand-breaks, apoptosis and increased cell proliferation [20,26,29].…”

Section: Introductionmentioning

confidence: 99%

Cyto-genotoxic effects of smoke from commercial filter and non-filter cigarettes on human bronchial and pulmonary cells

Cavallo

Ursini

Fresegna

et al. 2013

Mutation Research/Genetic Toxicology and Environmental Mutagene

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Clusterin Decreases Oxidative Stress in Lung Fibroblasts Exposed to Cigarette Smoke

Abstract: We conclude that clusterin may have a protective effect against cigarette smoke-induced oxidative stress in lung fibroblasts.

Cited by 41 publications

References 36 publications

Pathophysiology of the Small Airways in Chronic Obstructive Pulmonary Disease

Pathophysiology of the Small Airways in Chronic Obstructive Pulmonary Disease

The Aryl Hydrocarbon Receptor Attenuates Tobacco Smoke-induced Cyclooxygenase-2 and Prostaglandin Production in Lung Fibroblasts through Regulation of the NF-κB Family Member RelB

Cyto-genotoxic effects of smoke from commercial filter and non-filter cigarettes on human bronchial and pulmonary cells

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