The effects of cigarette smoke on airway inflammation in asthma and COPD: Therapeutic implications

Tamimi, Asad; Serdarevic, Dzelal; Hanania, Nicola A.

doi:10.1016/j.rmed.2011.11.003

Cited by 158 publications

(125 citation statements)

References 105 publications

(103 reference statements)

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“…These results are in line with clinical studies showing that RA smokers show a poor response to anti-TNF treatment and RA heavy smokers have the poorest drug survival [38]. At the cellular level, exposure to cigarette smoke was also shown to increase the production of TNFα in inflammatory cells in vitro [39][40][41]. However, as reported previously we could not detect TNFα expression in unstimulated or CSE treated RASF [34].…”

Section: Discussionsupporting

confidence: 91%

Regulation and function of SIRT1 in rheumatoid arthritis synovial fibroblasts

et al. 2015

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Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by inflammation and destruction of synovial joints. The function of sirtuin (SIRT)1 in RA is inconclusive. In human synovial cells, SIRT1 was shown to promote cytokine production and apoptosis resistance. However, deletion of SIRT1 aggravated inflammatory arthritis in mice and increased production of pro-inflammatory cytokines in murine macrophages. In the current study, we investigated the regulation, expression, and function of SIRT1 in RA, in particular its role in adhesion and proliferation of human RA synovial fibroblasts (RASF). We found that expression of SIRT1 was increased in vivo in synovial tissues of RA smokers and in vitro by stimulation of RASF with TNF, but decreased upon treatment with cigarette smoke extract. Synovial tissues of RA smokers showed higher leukocytic infiltration that positively correlated with enhanced levels of SIRT1. Global transcriptome analysis revealed that SIRT1 modulates expression of genes involved in the regulation of inflammatory response and cell adhesion. In functional studies, silencing of SIRT1 reduced proliferation and leukocytic adhesion to RASF but showed inconsistent results in the regulation of adhesion to plastic. In conclusion, SIRT1 modulates the proliferative and potentially also adhesive properties of RASF and can therefore promote progression of RA. KEY MESSAGES: SIRT1 is upregulated by TNF but decreased upon CSE treatment of RASF. Upregulation of SIRT1 in RA smokers correlates with increased leukocytic infiltration. SIRT1 modulates expression of genes regulating cell adhesion and inflammation. SIRT1 regulates proliferation of RASF. AbstractRheumatoid arthritis (RA) is a chronic autoimmune disease characterized by inflammation and destruction of synovial joints. The function of sirtuin (SIRT)1 in RA is inconclusive. In human synovial cells SIRT1 was shown to promote cytokine production and apoptosis resistance. However, deletion of SIRT1 aggravated inflammatory arthritis in mice and increased production of pro-inflammatory cytokines in murine macrophages. In the current study we investigated the regulation, expression and function of SIRT1 in RA, in particular its role in adhesion and proliferation of human RA synovial fibroblasts (RASF). We found that expression of SIRT1 was increased in vivo in synovial tissues of RA smokers and in vitro by stimulation of RASF with TNFα, but decreased upon treatment with cigarette smoke extract.Synovial tissues of RA smokers showed higher leukocytic infiltration that positively correlated with enhanced levels of SIRT1. Global transcriptome analysis revealed that SIRT1modulates expression of genes involved in the regulation of inflammatory response and cell adhesion. In functional studies, silencing of SIRT1 reduced proliferation and leukocytic adhesion to RASF, but showed inconsistent results in the regulation of adhesion to plastic. In conclusion, SIRT1 modulates the proliferative and potentially also adhesive properties of RASF and can t...

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Section: Discussionsupporting

confidence: 91%

Regulation and function of SIRT1 in rheumatoid arthritis synovial fibroblasts

et al. 2015

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“…In addition to oxidative stress, NF-B mediated pro-inflammatory responses to CS play a key role in the pathogenesis of chronic inflammatory lung diseases (Di Stefano et al, 2002;MacNee, 2005;Rahman and MacNee, 1998;Tamimi et al, 2012). Our laboratory previously found that ADMA induced oxidative and nitrosative stress in lung epithelial cells (Klein et al, 2010).…”

Section: Adma In Combination With Cse Increases Nf-jb Binding Activitmentioning

confidence: 99%

“…The exposure leads to the activation of endogenous oxidative processes, which in turn modulate the activity of redox-sensitive signal transduction pathways (Kou et al, 2011;Pacher et al, 2007). These pathways also include the transcription factor nuclear factor (NF)-B (Tamimi et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Asymmetric dimethyl-arginine metabolism in a murine model of cigarette smoke-mediated lung inflammation

Staab

Weigel

Xiao

et al. 2014

Journal of Immunotoxicology

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There is increasing evidence that the endogenous nitric oxide synthase (NOS) inhibitor asymmetric dimethyl-arginine (ADMA) is involved in the pathogenesis of chronic lung diseases. One important regulator of this molecule is the ADMA-metabolizing enzyme dimethyl-arginine dimethyl-aminohydrolase (DDAH). The objective of this study was to determine whether perturbation of the ADMA-DDAH pathway contributes to lung inflammation following exposure to cigarette smoke (CS). For these studies, wild-type and DDAH transgenic mice were sham or CS-exposed. Serum ADMA levels were determined by mass spectrometry. ADMA content and DDAH expression were also visualized in mouse lung tissue by immunohistochemistry. DDAH expression was determined by real-time quantitative PCR (qPCR). Inflammation was assessed by H&E staining and analyses of total cell counts and fluid tumor necrosis factor (TNF)-levels (using ELISA) in lung lavage fluid. NF-B binding activity in mouse lung epithelial (LA-4) cells was assessed by a transcription factor-binding assay. The results indicated that the concentration of serum ADMA was increased following exposure to CS, and this corresponded with increased ADMA content in bronchial epithelial cells in lung tissue. Total lung DDAH expression was significantly decreased in lung tissue and cultured LA-4 cells following CS exposure. Addition of exogenous ADMA increased CSE-mediated NF-B binding activity and TNFa production in LA-4 cells more than 2-fold compared to that in CSE-exposed controls. CS-mediated lung inflammation was significantly attenuated in DDAH transgenic mice compared to in wild-type controls. These findings demonstrated that lung ADMA metabolism was altered in mice following CS exposure and suggested that ADMA played a role in CS-mediated inflammation through increasing the presence of inflammatory mediators in lung epithelial cells.

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“…On the other hand, theophylline has a variety of favorable anti-inflammatory effects on eosinophils, including the suppression of superoxide production (Piacentini et al, 2005), migration (Kikuchi et al, 2007) and eosinophilopoiesis (Wang et al, 2003), and the induction of apoptosis (Chung et al, 2000). Theophylline has further been reported to increase the activity of histone deacetylase 2 (HDAC2) (Tamimi et al, 2012) and is expected to be effective in the treatment of smoking-induced asthma (Spears et al, 2009) and COPD (Cosio et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

Effects of inhaled aminophylline on airway constriction and inflammation in ovalbumin-sensitized guinea pigs

Muraki¹,

Wada²,

Ohno³

et al. 2013

Drug Delivery

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Background: The systemic administration of theophylline is useful for asthma treatment. However its narrow therapeutic range makes it difficult to use. Little is known about its potential in inhalation therapy, particularly repeated inhalation. Objective: The purpose of this study is to investigate the therapeutic usefulness of inhaled aminophylline in an asthma model. Methods: The effects of pretreatment with inhaled aminophylline (25 mg/mL for 30 min/dose) on airway response and inflammation after an ovalbumin (OVA) challenge and airway hypersensitivity to acetylcholine (Ach) were evaluated using guinea pigs sensitized with OVA. Results: Aminophylline relaxed the ACh-induced contraction of tracheal smooth muscle in vitro in a concentration-dependent manner. Pretreatment with single-dose aminophylline inhalation suppressed OVA-induced airway constriction to the same extent as the intraperitoneal pretreatment with high-dose aminophylline (10-20 mg/kg). However, pretreatment with singledose aminophylline inhalation did not suppress eosinophil infiltration into airways (neither bronchoalveolar lavage [BAL] fluid nor lung tissue) and did not suppress airway hyperreactivity to ACh, 24 h after OVA challenge. Repeated inhalation of aminophylline (twice daily for 7 days) suppressed the infiltration of eosinophils and suppressed airway hypersensitivity to ACh. In addition, high concentrations of aminophylline inhibited production of oxygen radicals by BAL cells. Conclusion: Single-dose inhalation treatment with aminophylline has transient but relatively strong bronchodilating effects due to delivery of high doses into local airways. Repeated inhalation treatment suppressed airway inflammation and hypersensitivity induced by allergens. Therefore, inhaled aminophylline may be useful for asthma treatment.

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The effects of cigarette smoke on airway inflammation in asthma and COPD: Therapeutic implications

Cited by 158 publications

References 105 publications

Regulation and function of SIRT1 in rheumatoid arthritis synovial fibroblasts

Regulation and function of SIRT1 in rheumatoid arthritis synovial fibroblasts

Asymmetric dimethyl-arginine metabolism in a murine model of cigarette smoke-mediated lung inflammation

Effects of inhaled aminophylline on airway constriction and inflammation in ovalbumin-sensitized guinea pigs

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