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      Anti-Inflammatory Effects of Lactobacillus Rahmnosus and Bifidobacterium Breve on Cigarette Smoke Activated Human Macrophages

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          Abstract

          Background

          Chronic obstructive pulmonary disease (COPD) is a major global health problem with cigarette smoke (CS) as the main risk factor for its development. Airway inflammation in COPD involves the increased expression of inflammatory mediators such as CXCL-8 and IL-1β which are important mediators for neutrophil recruitment. Macrophages are an important source of these mediators in COPD. Lactobacillus rhamnosus ( L. rhamnosus) and Befidobacterium breve ( B. breve) attenuate the development of ‘allergic asthma’ in animals but their effects in COPD are unknown.

          Objective

          To determine the anti-inflammatory effects of L. rhamnosus and B. breve on CS and Toll-like receptor (TLR) activation.

          Design

          We stimulated the human macrophage cell line THP-1 with CS extract in the presence and absence of L. rhamnosus and B. breve and measured the expression and release of inflammatory mediators by RT-qPCR and ELISA respectively. An activity assay and Western blotting were used to examine NF-κB activation.

          Results

          Both L. rhamnosus and B. breve were efficiently phagocytized by human macrophages. L. rhamnosus and B. breve significantly suppressed the ability of CS to induce the expression of IL-1β, IL-6, IL-10, IL-23, TNFα, CXCL-8 and HMGB1 release (all p<0.05) in human THP-1 macrophages. Similar suppression of TLR4- and TLR9-induced CXCL8 expression was also observed (p<0.05). The effect of L. rhamnosus and B. breve on inflammatory mediator release was associated with the suppression of CS-induced NF-κB activation (p<0.05).

          Conclusions

          This data indicate that these probiotics may be useful anti-inflammatory agents in CS-associated disease such as COPD.

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          Most cited references39

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          Mechanisms of probiotic actions - A review.

          Probiotics are gaining more and more interest as alternatives for antibiotics or anti-inflammatory drugs. However, their mode of action is poorly understood. This review will present examples of probiotic actions from three general modes of actions into which probiotic effects can be classified. Probiotics might modulate the host's immune system, affect other microorganisms directly or act on microbial products, host products or food components. What kind of effect(s) a certain probiotic executes depends on its metabolic properties, the molecules presented at its surface or on the components secreted. Even integral parts of the bacterial cell such as its DNA or peptidoglycan might be of importance for its probiotic effectiveness. The individual combination of such properties in a certain probiotic strain determines its specific probiotic action and as a consequence its effective application for the prevention and/or treatment of a certain disease. Copyright 2009 Elsevier GmbH. All rights reserved.
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            Recognition and signaling by toll-like receptors.

            Toll-like receptors (TLRs) are transmembrane proteins that detect invading pathogens by binding conserved, microbially derived molecules and that induce signaling cascades for proinflammatory gene expression. A critical component of the innate immune system, TLRs utilize leucine-rich-repeat motifs for ligand binding and a shared cytoplasmic domain to recruit the adaptors MyD88, TRIF, TIRAP, and/or TRAM for downstream signaling. Despite significant domain conservation, TLRs induce gene programs that lead not only to the robust production of general proinflammatory mediators but also to the production of unique effectors, which provide pathogen-tailored immune responses. Here we review the mechanisms by which TLRs recognize pathogens and induce distinct signaling cascades.
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              Pulmonary-intestinal cross-talk in mucosal inflammatory disease

              Chronic obstructive pulmonary disease (COPD) and inflammatory bowel diseases (IBD) are chronic inflammatory diseases of mucosal tissues that affect the respiratory and gastrointestinal tracts, respectively. They share many similarities in epidemiological and clinical characteristics as well as inflammatory pathologies. Importantly, both conditions are accompanied by systemic co-morbidities that are largely overlooked in both basic and clinical research. Therefore, consideration of these complications may maximise the efficacy of prevention and treatment approaches. Here, we examine both the intestinal involvement in COPD and the pulmonary manifestations of IBD. We also review the evidence for inflammatory organ cross-talk that may drive these associations, and discuss the current frontiers of research into these issues.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                28 August 2015
                2015
                : 10
                : 8
                : e0136455
                Affiliations
                [1 ]Cell and Molecular Biology Group, Airways Disease Section, National Heart and Lung Institute, Faculty of Medicine, Imperial College London, Dovehouse Street, London, United Kingdom
                [2 ]Chronic respiratory research center, National Research and Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
                [3 ]Department of Immunology, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
                [4 ]Department of Clinical and Biological Sciences, University of Torino, Torino, Italy
                [5 ]Mycobacteriology Research Center (MRC) National Research Institute of Tuberculosis and lung diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
                [6 ]Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, The Netherlands
                [7 ]Nutricia Research Centre for Specialized Nutrition, Utrecht, The Netherlands
                University of Rochester Medical Center, UNITED STATES
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: EM IMA JG GF. Performed the experiments: EM IMA. Analyzed the data: AAV MV HJ FLMR. Contributed reagents/materials/analysis tools: FLMR AAV MV. Wrote the paper: EM JG IMA MV.

                Article
                PONE-D-15-17341
                10.1371/journal.pone.0136455
                4552661
                26317628
                b6943001-7131-41da-bd62-8dc8b211ed3f
                Copyright @ 2015

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

                History
                : 21 April 2015
                : 3 August 2015
                Page count
                Figures: 6, Tables: 1, Pages: 17
                Funding
                IMA is supported by the MRC (G1001367/1), the Wellcome Trust (093080/Z/10/Z) and by Interuniversity Attraction Poles (IAP) Project P7/30. Research by IMA is also supported by the NIHR Respiratory Disease Biomedical Research Unit at the Royal Brompton NHS Foundation Trust and Imperial College London. EM is supported by an ERS Long Term Fellowship (LTRF 2013-2052). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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