Ian M Adcock

Imperial College London, Londinium, England, United Kingdom

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Publications (366)1781.65 Total impact

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    ABSTRACT: Tuberculosis (TB) is considered a major worldwide health problem with 10 million new cases diagnosed each year. Our understanding of TB immunology has become greater and more refined since the identification of Mycobacterium tuberculosis (MTB) as an etiologic agent and the recognition of new signaling pathways modulating infection. Understanding the mechanisms through which the cells of the immune system recognize MTB can be an important step in designing novel therapeutic approaches, as well as improving the limited success of current vaccination strategies. A great challenge in chronic disease is to understand the complexities, mechanisms, and consequences of host interactions with pathogens. Innate immune responses along with the involvement of distinct inflammatory mediators and cells play an important role in the host defense against the MTB. Several classes of pattern recognition receptors (PRRs) are involved in the recognition of MTB including Toll-Like Receptors (TLRs), C-type lectin receptors (CLRs) and Nod-like receptors (NLRs) linked to inflammasome activation. Among the TLR family, TLR1, TLR2, TLR4, and TLR9 and their down-stream signaling proteins play critical roles in the initiation of the immune response in the pathogenesis of TB. The inflammasome pathway is associated with the coordinated release of cytokines such as IL-1β and IL-18 which also play a role in the pathogenesis of TB. Understanding the cross-talk between these signaling pathways will impact on the design of novel therapeutic strategies and in the development of vaccines and immunotherapy regimes. Abnormalities in PRR signaling pathways regulated by TB will affect disease pathogenesis and need to be elucidated. In this review we provide an update on PRR signaling during M. tuberculosis infection and indicate how greater knowledge of these pathways may lead to new therapeutic opportunities.
    Journal of clinical immunology. 10/2014;
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    ABSTRACT: Abstract : Tuberculosis remains a major public health problem in most of the developing world and the emerging epidemic of acquired immunodeficiency syndrome has resulted in a resurgence of Tuberculosis throughout the world. Nontuberculous mycobacteria refers to all the species in the family of mycobacteria that may cause human disease, but do 56 not cause Tuberculosis. Every year in the world approximately two people per 100,000 populations develop infections caused by these lesser-known "cousins" of Tuberculosisand leprosy. In this study we focus on a rare case of a patient with chronic granulomatous disease presenting with both Mycobacterium Tuberculosis and 60 Nontuberculous mycobacteria. To our knowledge this is the first report of patient with carrier of chronic granulomatous disease combined with Mycobacterium Tuberculosis and Nontuberculous mycobacteria. The presented information may help to improve the diagnosis and open a new light in investigation of susceptibility of patients to mycobacterium infections.
    BioMed Research International 09/2014; · 2.71 Impact Factor
  • The European respiratory journal. 09/2014; 44(3):578-84.
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    ABSTRACT: Exposure to ozone (O3) has been associated with airway inflammation, oxidative stress and bronchial hyperresponsiveness (BHR). The goal of this study was to examine whether these adverse effects of ozone could be prevented or reversed by hydrogen sulfide (H2S) as a reducing agent. The H2S donor sodium hydrogen sulfide (NaHS) (2 mg/kg) or vehicle (PBS) was intraperitoneally injected into mice 1 hour before and after 3-hour ozone (2.5 ppm) or air exposure, and the mice were studied 24 hours later. Preventive and therapeutic treatment with NaHS reduced the ozone-induced increases in the total cells, including neutrophils and macrophages; this treatment also reduced levels of cytokines, including tumor necrosis factor-α (TNF-α), chemokine (C-X-C motif) ligand 1 (KC), interleukin-6 (IL-6) and interleukin-1β (IL-1β) levels in bronchial alveolar lavage (BAL) fluid; inhibited BHR; and attenuated ozone-induced increases in total malondialdehyde (MDA) in BAL fluid and decreases in the ratio of reduced glutathione/oxidized glutathione (GSH/GSSG) in the lung. Ozone exposure led to decreases in the H2S production rate and in mRNA and protein levels of cystathionine-β-synthetase (CBS) and cystathionine-γ-lyase (CSE) in the lung. These effects were prevented and reversed by NaHS treatment. Furthermore, NaHS prevented and reversed the phosphorylation of p38 mitogen-activated protein kinase (MAPK) and heat shock protein (HSP) 27. H2S may have both preventive and therapeutic value in the treatment of airway diseases that have an oxidative stress basis.
    American Journal of Respiratory Cell and Molecular Biology 07/2014; · 4.15 Impact Factor
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    ABSTRACT: Idiopathic pulmonary arterial hypertension (IPAH) is an incurable condition leading to right ventricular failure and death and inflammation is postulated to be associated with vascular remodelling. Interleukin (IL)-33, a member of the "alarmin" family can either act on the membrane ST2 receptor or as a nuclear repressor, to regulate inflammation. We show, using immunohistochemistry, that IL-33 expression is nuclear in the vessels of healthy subjects whereas nuclear IL-33 is markedly diminished in the vessels of IPAH patients. This correlates with reduced IL-33 mRNA expression in their lung. In contrast, serum levels of IL-33 are unchanged in IPAH. However, the expression of the soluble form of ST2, sST2, is enhanced in the serum of IPAH patients. Knock-down of IL-33 in human endothelial cells (ECs) using siRNA is associated with selective modulation of inflammatory genes involved in vascular remodelling including IL-6. Additionally, IL-33 knock-down significantly increased sST2 release from ECs. Chromatin immunoprecipitation demonstrated that IL-33 bound multiple putative homeodomain protein binding motifs in the proximal and distal promoters of ST2 genes. IL-33 formed a complex with the histone methyltransferase SUV39H1, a transcriptional repressor. In conclusion, IL-33 regulates the expression of IL-6 and sST2, an endogenous IL-33 inhibitor, in primary human ECs and may play an important role in the pathogenesis of PAH through recruitment of transcriptional repressor proteins.
    Biochemical and Biophysical Research Communications 07/2014; · 2.28 Impact Factor
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    European Respiratory Journal 06/2014; · 6.36 Impact Factor
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    European Respiratory Journal 06/2014; · 6.36 Impact Factor
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    ABSTRACT: Background The airway smooth muscle (ASM) cell maintains its own proliferative rate and contributes to the inflammatory response in the airways, effects that are inhibited by corticosteroids, used in the treatment of airways diseases. Objective We determined the differential expression of mRNAs, microRNAs (miRNAs) and long noncoding RNA species (lncRNAs) in primary ASM cells following treatment with a corticosteroid, dexamethasone, and fetal calf serum (FCS). Methods mRNA, miRNA and lncRNA expression was measured by microarray and quantitative real-time PCR. Results A small number of miRNAs (including miR-150, -371-5p, -718, -940, -1181, -1207-5p, -1915, and -3663-3p) were decreased following exposure to dexamethasone and FCS. The mRNA targets of these miRNAs were increased in expression. The changes in mRNA expression were associated with regulation of ASM actin cytoskeleton. We also observed changes in expression of lncRNAs, including natural antisense, pseudogenes, intronic lncRNAs, and intergenic lncRNAs following dexamethasone and FCS. We confirmed the change in expression of three of these, LINC00882, LINC00883, PVT1, and its transcriptional activator, c-MYC. We propose that four of these lincRNAs (RP11-46A10.4, LINC00883, BCYRN1, and LINC00882) act as miRNA 'sponges' for 4 miRNAs with decreased expression (miR-150, -371-5p, -940, -1207-5p). Conclusion This in-vitro model of primary ASM cell phenotype was associated with the regulation of several ncRNAs. Their identification allows for in-vitro functional experimentation to establish causality with the primary ASM phenotype, and in airway diseases such as asthma and chronic obstructive pulmonary disease (COPD).
    Respiratory Research 05/2014; · 3.13 Impact Factor
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    ABSTRACT: Abstract Objective: Asthma is an inflammatory airway disease, characterized by airway eosinophilia, in which CCL11 (eotaxin) plays a crucial role. The aim of study is to determine the elevation of CCL11 levels in bronchoalveolar lavage fluid (BALF), blood, exhaled breath condensate (EBC) and sputum in asthma patients and to identify which medium yields the most significant change in CCL11 level. Methods: The databases of PubMed, Embase and Cochrane Centre Register of Controlled Trials were systematically searched from inception to September 2013. Controlled clinical trials that focused on CCL11 concentrations in asthma patients and controls, and their correlations with other asthma indicators were obtained. Data were analysed using Stata 12.0. Results: Thirty studies were included in this investigation. CCL11 levels in blood, EBC and sputum were significantly higher in asthma patients than in healthy subjects. Sputum CCL11 concentrations were significantly elevated in unstable asthma patients versus stable asthma patients and in uncontrolled asthma patients versus partially controlled asthma patients. CCL11 levels in sputum and blood were negatively correlated with the lung function as measured by FEV1%predicted, and were positively correlated with BALF, EBC and sputum eosinophil counts. Similarly, CCL11 concentrations were positively correlated with eosinophil cationic protein in EBC, blood and sputum as well as with interleukin-5 in sputum and fractional exhaled nitric oxide in EBC. Steroid treatment had no significant effect on CCL11 levels. Conclusions: CCL11 is a potentially useful biomarker for the diagnosis and assessment of asthma severity and control, especially in sputum. CCL11 is crucial in eosinophil chemoattraction and activation in asthma pathogenesis. Further studies using anti-CCL11 approaches are needed to confirm a role for CCL11 in asthma pathogenesis particularly in patients with more severe disease.
    Journal of Asthma 05/2014; · 1.85 Impact Factor
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    ABSTRACT: Oxidative stress, a pathogenetic factor in many conditions, including chronic obstructive pulmonary disease, arises due to accumulation of reactive oxygen species and defective antioxidant defenses in the lungs. The latter is due, at least in part, to impaired activation of NF-E2-related factor 2 (Nrf2), a transcription factor involved in the activation of antioxidant and cytoprotective genes. The bromodomain and extraterminal (BET) proteins, Brd2, Brd3, Brd4, and BrdT, bind to acetylated lysine residues on histone or nonhistone proteins recruiting transcriptional regulators and thus activating or repressing gene transcription. We investigated whether BET proteins modulate the regulation of Nrf2-dependent gene expression in primary human airway smooth muscle cells and the human monocytic cell line, THP-1. Inhibition of BET protein bromodomains using the inhibitor JQ1+ or attenuation of Brd2 and Brd4 expression using small interfering RNA led to activation of Nrf2-dependent transcription and expression of the antioxidant proteins heme oxygenase-1, NADPH quinone oxidoreductase 1, and glutamate-cysteine ligase catalytic subunit. Also, JQ1+ prevented H2O2-induced intracellular reactive oxygen species production. By coimmunoprecipitation, BET proteins were found to be complexed with Nrf2, whereas chromatin-immunoprecipitation studies indicated recruitment of Brd2 and Brd4 to Nrf2-binding sites on the promoters of heme oxygenase-1 and NADPH quinone oxidoreductase 1. BET proteins, particularly Brd2 and Brd4, may play a key role in the regulation of Nrf2-dependent antioxidant gene transcription and are hence an important target for augmenting antioxidant responses in oxidative stress-mediated diseases.
    The Journal of Immunology 04/2014; · 5.52 Impact Factor
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    ABSTRACT: Tuberculosis (TB) is caused by infection with Mycobacterium tuberculosis (M. Tuberculosis, MTB) and despite ongoing global efforts for its eradication there were still an estimated 8.7 million new cases and 1.4 million deaths worldwide in 2011 (1). Co-infection with HIV caused 13% new actively infected people resulting in a high mortality rate (48.6 %) among these patients (2). TB is therefore considered as one of the leading causes of death due to infectious diseases worldwide despite the availability of effective and extensive therapeutic approaches (3, 4). Two TB-related conditions have been reported, namely, active TB and a latent form of TB infection whereby MTB survives in the body without causing overt signs or symptoms of the disease. People with latent TB infection are not infectious and cannot spread the TB bacteria to others. However, if TB bacteria become active in the body and multiply, the person will go from having a latent TB infection to being sick with TB disease and becoming infective. This unmasking of the latent disease may be idiopathic or the result of immunosuppression either from disease directly or from the use of drugs for treatment of other diseases (5). The first line of defense against MTB is provided by alveolar macrophages, which ingest and sequester the bacilli within granulomatous structures. The control and resolution of the infection also require activated T lymphocytes (6) and Th 1 cytokines (7). Interestingly, genetic defects within the IL-12/IFN− pathway have been found in patients with mendelian susceptibility to mycobacterial disease (MSMD) caused by live BCG vaccine or NTM species. This highlights the crucial role of IL-12/IFN− axis in the immune regulation of TB (8). Sarcoidosis is considered an autoimmune disease characterized by multisystem disorder of unclear etiology that involves any organ, but most commonly the lungs and the intrathoracic lymph nodes although the heart, skin and central nervous system are frequently affected (9). Despite the first clinical description of sarcoidosis over 120 years ago, little is known about the pathogenesis of this disease (10). A genetic predisposition to sarcoidosis is evident from epidemiological studies of familial aggregation, differences in disease susceptibility and severity between racial groups and the significantly increased incidence of sarcoidosis in monozygotic twins of affected individuals compared to other siblings (11, 12). More recent results have provided further insights into the genetic risks for TANAFFOS
    Tanaffos 03/2014;
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    ABSTRACT: Airway inflammation, especially neutrophilic airway inflammation, is a cardinal pathophysiologic feature in chronic obstructive pulmonary disease (COPD) patients. The ideal biomarkers characterizing the inflammation might have important potential clinical applications in disease assessment and therapeutic intervention. Sputum myeloperoxidase (MPO) is recognized as a marker of neutrophil activity. The purpose of this meta-analysis is to determine whether sputum MPO levels could reflect disease status or be regulated by regular medications for COPD. Studies were identified by searching PubMed, Embase, the Cochrane Database, CINAHL and www.controlled-trials.com for relevant reports published before September 2012. Observational studies comparing sputum MPO in COPD patients and healthy subjects or asthmatics, or within the COPD group, and studies comparing sputum MPO before and after treatment were all included. Data were independently extracted by two investigators and analyzed using STATA 10.0 software. A total of 24 studies were included in the meta-analysis. Sputum MPO levels were increased in stable COPD patients when compared with normal controls, and this increase was especially pronounced during exacerbations as compared with MPO levels during the stable state. Theophylline treatment was able to reduce MPO levels in COPD patients, while glucocorticoid treatment failed to achieve the same result. Sputum MPO might be a promising biomarker for guiding COPD management; however, further investigations are needed to confirm this.
    European journal of medical research. 03/2014; 19(1):12.
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    ABSTRACT: To the Editor:Hydrogen sulfide (H2S) has emerged as a new and important endogenous regulator of inflammation in recent years (1) and may also protect from emphysema induced by cigarette smoke exposure (2). We have also recently shown that H2S can inhibit airway smooth muscle cell proliferation and inflammatory mediator release in vitro (3). Serum levels of H2S positively correlate with the decline in lung function in chronic obstructive pulmonary disease (COPD) and were significantly lower in Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage III patients compared with those in GOLD I (4). Existing therapies for COPD, such as corticosteroids or long-acting anticholinergic agents, may reduce the exacerbation rate but do not significantly slow disease progression. A previous study has shown that theophylline alone had no impact on serum H2S levels and is of limited value in the management of stable COPD (5). Interestingly, sputum H2S measured in patients with asthma correlated with sputum neutrophil counts and the degree of airflow obstruction measured by forced expiratory volume in 1 s (FEV1) % predicted (6). Moreover, combination therapy of an inhaled glucocorticoid with low-dose theophylline has been shown to attenuate airway inflammation in patients with COPD and reverse glucocorticoid resistance (7). We.
    European Respiratory Journal 02/2014; · 6.36 Impact Factor
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    ABSTRACT: The immunopathology of sarcoidosis remains elusive despite years of research into this multiorgan disease.However, recent studies have provided new insights into the genetics and immune components involved in the clinical manifestation of the disease. Granulomatous inflammation is due to the host immune response to a persistent poorly degradable unknown antigen.Mycobacterium tuberculosis (MTB) is the major disease driver in many patients. The immune mechanisms that cause this disease start with the antigenic stimulus, followed by T-cell, macrophage and dendritic cell activation via a classic MHC II–mediated pathway. In addition, the profile of immune mediators reported in sarcoidosis indicates that the inflammasome pathway plays a critical role in disease pathogenesis. Increased understanding of the signal transductions pathways involved in the induction of inflammatory processes in sarcoidosis could give rise to new therapeutic approaches in future.
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    ABSTRACT: The use of flow cytometry in the clinical laboratory has grown substantially in the past decade. Flow cytometry provides rapid analysis of multiple characteristics of single cells. The information obtained by flow cytometry is both qualitative and quantitative. For example, it is possible to detect the cell size and granularity and aspects of DNA and RNA content which are used to characterize the phenotype of single cells. Moreover, flow cytometry is used for immunophenotyping of a variety of specimens, including whole blood, bone marrow, serous cavity fluids, CSF, urine and all types of body fluids. The technique has also been applied to human bronchoalveolar lavage (BAL) fluid, peritoneal fluids and blood. In this review paper, we update the recent findings regarding to the application of flow cytometry as a diagnostic tool in various lung diseases. We focus on the analysis of composition of BAL cells in chronic obstructive lung disease (COPD), asthma, lung cancer, sarcoidosis, tuberculosis and idiopathic eosinophilic pneumonia (IEP).
    Iranian journal of allergy, asthma, and immunology 01/2014; · 0.65 Impact Factor
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    ABSTRACT: In models of COPD, environmental stressors induce innate immune responses, inflammasome activation and inflammation. However, the interaction between these responses and their role in driving pulmonary inflammation in stable COPD is unknown. To investigate the activation of innate immunity and inflammasome pathways in the bronchial mucosa and bronchoalveolar lavage (BAL) of patients with stable COPD of different severity and control healthy smokers and non-smokers. Innate immune mediators (interleukin (IL)-6, IL-7, IL-10, IL-27, IL-37, thymic stromal lymphopoietin (TSLP), interferon γ and their receptors, STAT1 and pSTAT1) and inflammasome components (NLRP3, NALP7, caspase 1, IL-1β and its receptors, IL-18, IL-33, ST2) were measured in the bronchial mucosa using immunohistochemistry. IL-6, soluble IL-6R, sgp130, IL-7, IL-27, HMGB1, IL-33, IL-37 and soluble ST2 were measured in BAL using ELISA. In bronchial biopsies IL-27+ and pSTAT1+ cells are increased in patients with severe COPD compared with control healthy smokers. IL-7+ cells are increased in patients with COPD and control smokers compared with control non-smokers. In severe stable COPD IL-7R+, IL-27R+ and TSLPR+ cells are increased in comparison with both control groups. The NALP3 inflammasome is not activated in patients with stable COPD compared with control subjects. The inflammasome inhibitory molecules NALP7 and IL-37 are increased in patients with COPD compared with control smokers. IL-6 levels are increased in BAL from patients with stable COPD compared with control smokers with normal lung function whereas IL-1β and IL-18 were similar across all groups. Increased expression of IL-27, IL-37 and NALP7 in the bronchial mucosa may be involved in progression of stable COPD.
    Thorax 01/2014; · 8.38 Impact Factor
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    ABSTRACT: Currently, there is no cure for chronic obstructive pulmonary disease (COPD). The limited efficacy of current therapies for COPD indicates a pressing need to develop new treatments to prevent the progression of the disease, which consumes a significant amount of health care resources and is an important cause of mortality worldwide. Current national and international guidelines for the management of stable COPD patients recommend the use of inhaled long-acting bronchodilators, inhaled corticosteroids, and their combination for maintenance treatment of moderate to severe stable COPD. Once-daily fluticasone furoate/vilanterol dry powder inhaler combination therapy has recently been approved by the US Food and Drug Administration and the European Medicines Agency as a new regular treatment for patients with stable COPD. Fluticasone furoate/vilanterol dry powder inhaler combination therapy has been shown to be effective in many controlled clinical trials involving thousands of patients in the regular treatment of stable COPD. This is the first once-daily combination of ultra-long-acting inhaled β2-agonists and inhaled glucocorticoids that is available for the treatment of stable COPD and has great potential to improve compliance to long-term regular inhaled therapy and hence to improve the natural history and prognosis of COPD patients.
    International Journal of COPD 01/2014; 9:249-256.
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    ABSTRACT: Eosinophils play a central role in asthma. The present study was performed to investigate the effect of tumour necrosis factor-α (TNF-α) on longevity of isolated human eosinophils. In contrast to Fas, TNF-α inhibited eosinophil apoptosis as evidenced by a combination of flow cytometry, DNA fragmentation assay and morphological analyses. The effect of TNF-α on eosinophil apoptosis was reversed by a TNF-α neutralising antibody. The anti-apoptotic effect of TNF-α was not due to autocrine release of known survival-prolonging cytokines interleukins 3 and 5 or granulocyte-macrophage-colony-stimulating factor as their neutralisation did not affect the effect of TNF-α. The anti-apoptotic signal was mediated mainly by the TNF-receptor 1. TNF-α induced phosphorylation and degradation of IκB and an increase in NF-κB DNA-binding activity. The survival-prolonging effect of TNF-α was reversed by inhibitors of NF-κB pyrrolidinedithiocarbamate and gliotoxin and by an inhibitor of IκB kinase, BMS-345541. TNF-α induced also an increase in AP-1 DNA-binding activity and the antiapoptotic effect of TNF-α was potentiated by inhibitors of AP-1, SR 11302 and tanshinone IIA and by an inhibitor of c-jun-N-terminal kinase, SP600125, which is an upstream kinase activating AP-1. Our results thus suggest that TNF-α delays human eosinophil apoptosis via TNF-receptor 1 and the resulting changes in longevity depend on yin-yang balance between activation of NF-κB and AP-1.
    PLoS ONE 01/2014; 9(2):e90298. · 3.53 Impact Factor
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    ABSTRACT: Chronic inflammation and oxidative stress are key features of chronic obstructive pulmonary disease (COPD). Oxidative stress enhances COPD inflammation under the control of the pro-inflammatory redox-sensitive transcription factor nuclear factor-kappaB (NF-κB). Histone acetylation plays a critical role in chronic inflammation and bromodomain and extra terminal (BET) proteins act as "readers" of acetylated histones. Therefore, we examined the role of BET proteins in particular Brd2 and Brd4 and their inhibitors (JQ1 and PFI-1) in oxidative stress- enhanced inflammation in human bronchial epithelial cells. Human primary epithelial (NHBE) cells and BEAS-2B cell lines were stimulated with IL-1β (inflammatory stimulus) in the presence or absence of H2O2 (oxidative stress) and the effect of pre-treatment with bromodomain inhibitors (JQ1 and PFI-1) was investigated. Pro-inflammatory mediators (CXCL8 and IL-6) were measured by ELISA and transcripts by RT-PCR. H3 and H4 acetylation and recruitment of p65 and Brd4 to the native IL-8 and IL-6 promoters was investigated using chromatin immunoprecipitation (ChIP). The impact of Brd2 and Brd4 siRNA knockdown on inflammatory mediators was also investigated. H2O2 enhanced IL1β-induced IL-6 and CXCL8 expression in NHBE and BEAS-2B cells whereas H2O2 alone did not have any affect. H3 acetylation at the IL-6 and IL-8 promoters was associated with recruitment of p65 and Brd4 proteins. Although p65 acetylation was increased this was not directly targeted by Brd4. The BET inhibitors JQ1 and PFI-1 significantly reduced IL-6 and CXCL8 expression whereas no effect was seen with the inactive enantiomer JQ1(-). Brd4, but not Brd2, knockdown markedly reduced IL-6 and CXCL8 release. JQ1 also inhibited p65 and Brd4 recruitment to the IL-6 and IL-8 promoters. Oxidative stress enhanced IL1β-induced IL-6 and CXCL8 expression was significantly reduced by Brd4 inhibition. Brd4 plays an important role in the regulation of inflammatory genes and provides a potential novel anti-inflammatory target.
    PLoS ONE 01/2014; 9(4):e95051. · 3.53 Impact Factor
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    ABSTRACT: Cytokines play an important part in many pathobiological processes of chronic obstructive pulmonary disease (COPD), including the chronic inflammatory process, emphysema, and altered innate immune response. Proinflammatory cytokines of potential importance include tumor necrosis factor (TNF)-α, interferon-γ, interleukin (IL)-1β, IL-6, IL-17, IL-18, IL-32, and thymic stromal lymphopoietin (TSLP), and growth factors such as transforming growth factor-β. The current objectives of COPD treatment are to reduce symptoms, and to prevent and reduce the number of exacerbations. While current treatments achieve these goals to a certain extent, preventing the decline in lung function is not currently achievable. In addition, reversal of corticosteroid insensitivity and control of the fibrotic process while reducing the emphysematous process could also be controlled by specific cytokines. The abnormal pathobiological process of COPD may contribute to these fundamental characteristics of COPD, and therefore targeting cytokines involved may be a fruitful endeavor. Although there has been much work that has implicated various cytokines as potentially playing an important role in COPD, there have been very few studies that have examined the effect of specific cytokine blockade in COPD. The two largest studies that have been reported in the literature involve the use of blocking antibody to TNFα and CXCL8 (IL-8), and neither has provided benefit. Blocking the actions of CXCL8 through its CXCR2 receptor blockade was not successful either. Studies of antibodies against IL-17, IL-18, IL-1β, and TSLP are currently either being undertaken or planned. There is a need to carefully phenotype COPD and discover good biomarkers of drug efficacy for each specific target. Specific groups of COPD patients should be targeted with specific anticytokine therapy if there is evidence of high expression of that cytokine and there are features of the clinical expression of COPD that will respond.
    International Journal of COPD 01/2014; 9:397-412.

Publication Stats

14k Citations
1,781.65 Total Impact Points


  • 1996–2014
    • Imperial College London
      • • Section of Airway Disease
      • • Division of Cell and Molecular Biology
      Londinium, England, United Kingdom
  • 1993–2014
    • National Heart, Lung, and Blood Institute
      Maryland, United States
  • 2010–2013
    • Nanjing Medical University
      • • Department of Respiratory Medicine
      • • Department of Respiratory Disease
      Nan-ching, Jiangsu Sheng, China
    • The University of Edinburgh
      • MRC Centre for Inflammation Research
      Edinburgh, SCT, United Kingdom
  • 2003–2013
    • Universita degli studi di Ferrara
      • • Research Center for the Research of Asthma and BPCO
      • • Department of Morphology, Surgery and Experimental Medicine
      Ferrara, Emilia-Romagna, Italy
  • 2012
    • Kinki University
      Ōsaka, Ōsaka, Japan
    • University Hospital Regensburg
      Ratisbon, Bavaria, Germany
  • 2009–2012
    • Utrecht University
      • Utrecht Institute for Pharmaceutical Sciences
      Utrecht, Utrecht, Netherlands
  • 2010–2011
    • Università degli Studi di Salerno
      • Department of BioMedical and Pharmaceutical Sciences FARMABIOMED
      Fisciano, Campania, Italy
  • 2008
    • University of Wisconsin–Madison
      Madison, Wisconsin, United States
    • Erciyes Üniversitesi
      Caesarea, Kayseri, Turkey
  • 2006
    • University Center Rochester
      • Department of Environmental Medicine
      Rochester, Minnesota, United States
  • 1993–2006
    • The Heart Lung Center
      Londinium, England, United Kingdom
  • 2005
    • Hospital Son Dureta
      Palma, Balearic Islands, Spain
  • 2004
    • University of Cologne
      • Division of Cardiology, Pneumology, Angiology and Intensive Care
      Köln, North Rhine-Westphalia, Germany
  • 2002
    • Fondazione Salvatore Maugeri IRCCS
      Ticinum, Lombardy, Italy
  • 2001
    • Chang Gung Memorial Hospital
      • Division of Thoracic Medicine
      Taipei, Taipei, Taiwan