Peroxisome Proliferator-Activated Receptor alpha (PPAR alpha) down-regulation in cystic fibrosis lymphocytes

Background: PPARs exhibit anti-inflammatory capacities and are potential modulators of the inflammatory response. We hypothesized that their expression and/or function may be altered in cystic fibrosis (CF), a disorder characterized by an excessive host inflammatory response. Methods: PPARα, β and γ mRNA levels were measured in peripheral blood cells of CF patients and healthy subjects via RT-PCR. PPARα protein expression and subcellular localization was determined via western blot and immunofluorescence, respectively. The activity of PPARα was analyzed by gel shift assay. Results: In lymphocytes, the expression of PPARα mRNA, but not of PPARβ, was reduced (-37%; p < 0.002) in CF patients compared with healthy persons and was therefore further analyzed. A similar reduction of PPARα was observed at protein level (-26%; p < 0.05). The transcription factor was mainly expressed in the cytosol of lymphocytes, with low expression in the nucleus. Moreover, DNA binding activity of the transcription factor was 36% less in lymphocytes of patients (p < 0.01). For PPARα and PPARβ mRNA expression in monocytes and neutrophils, no significant differences were observed between CF patients and healthy persons. In all cells, PPARγ mRNA levels were below the detection limit. Conclusion: Lymphocytes are important regulators of the inflammatory response by releasing cytokines and antibodies. The diminished lymphocytic expression and activity of PPARα may therefore contribute to the inflammatory processes that are observed in CF

Maternal allergic contact dermatitis causes increased asthma risk in offspring

<p>Abstract</p> <p>Background</p> <p>Offspring of asthmatic mothers have increased risk of developing asthma, based on human epidemiologic data and experimental animal models. The objective of this study was to determine whether maternal allergy at non-pulmonary sites can increase asthma risk in offspring.</p> <p>Methods</p> <p>BALB/c female mice received 2 topical applications of vehicle, dinitrochlorobenzene, or toluene diisocyanate before mating with untreated males. Dinitrochlorobenzene is a skin-sensitizer only and known to induce a Th1 response, while toluene diisocyanate is both a skin and respiratory sensitizer that causes a Th2 response. Both cause allergic contact dermatitis. Offspring underwent an intentionally suboptimal protocol of allergen sensitization and aerosol challenge, followed by evaluation of airway hyperresponsiveness, allergic airway inflammation, and cytokine production. Mothers were tested for allergic airway disease, evidence of dermatitis, cellularity of the draining lymph nodes, and systemic cytokine levels. The role of interleukin-4 was also explored using interleukin-4 deficient mice.</p> <p>Results</p> <p>Offspring of toluene diisocyanate but not dinitrochlorobenzene-treated mothers developed an asthmatic phenotype following allergen sensitization and challenge, seen as increased Penh values, airway inflammation, bronchoalveolar lavage total cell counts and eosinophilia, and Th2 cytokine imbalance in the lung. Toluene diisocyanate treated interleukin-4 deficient mothers were able to transfer asthma risk to offspring. Mothers in both experimental groups developed allergic contact dermatitis, but not allergic airway disease.</p> <p>Conclusion</p> <p>Maternal non-respiratory allergy (Th2-skewed dermatitis caused by toluene diisocyanate) can result in the maternal transmission of asthma risk in mice.</p

Activated MCTC mast cells infiltrate diseased lung areas in cystic fibrosis and idiopathic pulmonary fibrosis

<p>Abstract</p> <p>Background</p> <p>Although mast cells are regarded as important regulators of inflammation and tissue remodelling, their role in cystic fibrosis (CF) and idiopathic pulmonary fibrosis (IPF) has remained less studied. This study investigates the densities and phenotypes of mast cell populations in multiple lung compartments from patients with CF, IPF and never smoking controls.</p> <p>Methods</p> <p>Small airways, pulmonary vessels, and lung parenchyma were subjected to detailed immunohistochemical analyses using lungs from patients with CF (20 lung regions; 5 patients), IPF (21 regions; 7 patients) and controls (16 regions; 8 subjects). In each compartment the densities and distribution of MC_Tand MC_TCmast cell populations were studied as well as the mast cell expression of IL-6 and TGF-β.</p> <p>Results</p> <p>In the alveolar parenchyma in lungs from patients with CF, MC_TCnumbers increased in areas showing cellular inflammation or fibrosis compared to controls. Apart from an altered balance between MC_TCand MC_Tcells, mast cell in CF lungs showed elevated expression of IL-6. In CF, a decrease in total mast cell numbers was observed in small airways and pulmonary vessels. In patients with IPF, a significantly elevated MC_TCdensity was present in fibrotic areas of the alveolar parenchyma with increased mast cell expression of TGF-β. The total mast cell density was unchanged in small airways and decreased in pulmonary vessels in IPF. Both the density, as well as the percentage, of MC_TCcorrelated positively with the degree of fibrosis. The increased density of MC_TC, as well as MC_TCexpression of TGF-β, correlated negatively with patient lung function.</p> <p>Conclusions</p> <p>The present study reveals that altered mast cell populations, with increased numbers of MC_TCin diseased alveolar parenchyma, represents a significant component of the histopathology in CF and IPF. The mast cell alterations correlated to the degree of tissue remodelling and to lung function parameters. Further investigations of mast cells in these diseases may open for new therapeutic strategies.</p

Elevated expression of both mRNA and protein levels of IL-17A in sputum of stable Cystic Fibrosis patients

<p>Abstract</p> <p>Background</p> <p>T helper 17 (Th17) cells can recruit neutrophils to inflammatory sites through production of IL-17, which induces chemokine release. IL-23 is an important inducer of IL-17 and IL-22 production. Our aim was to study the role of Th17 cells in cystic fibrosis (CF) lung disease by measuring IL-17 protein and mRNA levels and IL-22 and IL-23 mRNA in sputum of clinically stable CF patients and by comparing these levels with healthy controls.</p> <p>Methods</p> <p>Sputum induction was performed in adult CF patients outside of an exacerbation and healthy control subjects. IL-17A protein levels were measured in supernatants with cytometric bead array (CBA) and RNA was isolated and quantitative RT-PCR was performed for IL-17A, IL-22 and IL-23.</p> <p>Results</p> <p>We found significantly higher levels of IL-17A protein and mRNA levels (both: p < 0.0001) and IL-23 mRNA levels (p < 0.0001) in the sputum of CF group as compared to controls. We found very low levels of IL-22 mRNA in the CF group. The levels of IL-17 and IL-23 mRNA were higher in patients chronically infected with <it>Pseudomonas aeruginosa </it>(<it>P. aeruginosa</it>) as compared to those who were not chronically infected with <it>P. aeruginosa</it>. The presence of <it>Staphylococcus aureus </it>(<it>S. aureus</it>) on sputum did not affect the IL-17 or IL-23 levels. There was no correlation between IL-17 or IL-23 levels and FEV₁nor sputum neutrophilia.</p> <p>Conclusion</p> <p>The elevated levels of IL-17 and IL-23 might indicate that Th17 cells are implicated in the persistent neutrophil infiltration in CF lung disease and chronic infection with <it>P. aeruginosa</it>.</p

Exploring the contribution of alternative food networks to food security. A comparative analysis

[EN] Food (in)security has become a challenge not only for developing economies but also for High Income Countries. In parallel, food scholars have actively investigated the contribution of alternative food networks (AFNs) to the development of more sustainable and just food systems, paying attention to drivers, initiatives and policies supporting the development of alternatives to the dominant industrialised food system and its detrimental environmental and socio-economic impacts. However, few studies have directly addressed the contribution of AFNs to food security in the Global North. This paper aims to establish new linkages between food security debates and critical AFNs literature. For that purpose, we conduct a place-based approach to food security in a comparative analysis of initiatives of three different European contexts: Cardiff city-region (UK), the Flemish Region (Belgium) and the peri-urban area of the city of Valencia (Spain). The results unfold: i) how AFNs weave a more localised socio-economic fabric that creates new relationships between food security outcomes and specific territories, ii) hybridization processes within alternative but also conventional systems and iii) the role of advocacy and collective action at different levels. The analysis allows identification of key elements on which food security debates hinge and provides new insights to ground conceptual discussions on territorial and place-based food security approaches.This research is part of the project "Assessment of the impact of global drivers of change on Europe's food security" (TRANSMANGO), granted by the EU under 7th Framework Programme; theme KBBE.2013.2.5-01; Grant agreement no: 613532. Dr. Ana Moragues-Faus also acknowledges the funding of the European Commission and the Welsh Government that currently supports her Ser Cymru fellowship. These results reflect only the authors' view; the funders are not liable for any use that may be made of the information contained therein.Cerrada-Serra, P.; Moragues-Faus, A.; Zwart, TA.; Adlerova, B.; Ortiz-Miranda, D.; Avermaete, T. (2018). Exploring the contribution of alternative food networks to food security. A comparative analysis. Food Security. 10(6):1371-1388. https://doi.org/10.1007/s12571-018-0860-xS13711388106Arcuri, S., Brunori, G., & Galli, F. (2017). Insights on the role of private and public actors in food assistance provision: A literature review for high income countries. Economia agro-alimentare. https://doi.org/10.3280/ECAG2017-001006 .Barca, F., McCann, P., & Rodríguez-Pose, A. (2012). The case for regional development intervetion: Place-based versus place-neutral approaches. Journal of Regional Science, 52, 134–152. https://doi.org/10.1111/j.1467-9787.2011.00756.x .Bauler, T., Mutombo, E., van Gameren, V., Crivits, M., Paredis, E., Boulanger, P., . . . Ruwet, C., (2011). Construction of scenarios and exploration of transition pathways for sustainable consumption patterns. Brussels: Belgian Science Policy.Brown, J. C., & Purcell, M. (2005). There’s nothing inherent about scale: Political ecology, the local trap, and the politics of development in the Brazilian Amazon. Geoforum, 36, 607–624. https://doi.org/10.1016/j.geoforum.2004.09.001 .Bourne, N. (2012) Fruit and vegetable community co-ops rise to 350 in Wales, BBC Wales News, Available at http://www.bbc.co.uk/news/uk-wales-17938418 . Accessed Sept 2017.Brunori, G., Malandrin, V., & Rossi, A. (2013). Trade-off or convergence? The role of food security in the evolution of food discourse in Italy. Journal of Rural Studies, 29, 19–29. https://doi.org/10.1016/j.jrurstud.2012.01.013 .Cistulli, V., Rodríguez-Pose, A., Escobar, G., Marta, S., & Schejtman, A. (2014). Addressing food security and nutrition by means of a territorial approach. Food Security, 6, 879–894. https://doi.org/10.1007/s12571-014-0395-8 .Clay, E. (2002). Food security; concept and measurement. Paper for FAO expert consultation on trade and food security: Conceptualising the linkages. Rome http://www.fao.org/docrep/005/y4671e/y4671e06.htm . Accessed Sept 2017.Cox, I. (2015). Interim report: Adding value and demonstrating sustainable development in the community food co-ops in Wales, EcoStudio.Crivits, M., & Paredis, E. (2013). Designing an explanatory practice framework: Local food systems as a case. Journal of Consumer Culture, 13, 306–336. https://doi.org/10.1177/1469540513484321joc.sagepub.com .CSM (2016). Connecting small-holders to farmers: an analytical guide.Dedeurwaedere, T., de Schutter, O., Hudon, M., Mathijs, E., Annaert, B., Avermaete, T., et al. (2015). Working paper: Social enterprise based transition movements between transformation and reform. The case of transition initiatives in local food networks. BRAIN-be. Food4Sustainability annual report 2. Deliverable 2.2.Dixon, J., & Richards, C. (2016). On food security and alternative food networks: Understanding and performing food security in the context of urban bias. Agriculture and Human Values, 33, 191–202. https://doi.org/10.1007/s10460-015-9630-y .Ekers, M., Levkoe, C. Z., Walker, S., & Dale, B. (2015). Will work for food: Agricultural interns, apprentices, volunteers, and the agrarian question. Agriculture and Human Values, 33, 705–720. https://doi.org/10.1007/s10460-015-9660-5 .Elliott, E., Parry, O., Ashdown-Lambert, J. (2004). Evaluation of community food co-ops, Working Paper 85, Cardiff School of Social Sciences, Cardiff University.FAO (1998). Report: Sustaining agricultural biodiversity and agro-ecosystem functions. http://www.fao.org/sd/EPdirect/EPre0080.htm . Accessed Nov 2017.FAO (2001). Report: The state of food insecurity in the world. http://www.fao.org/docrep/003/y1500e/y1500e00.htm . Accessed Nov 2017.Gibson-Graham, J. K. (2006). A postcapitalist politics. Minessota: University of Minnesota Press.Goodman, M. K. (2004). Reading fair trade: Political ecological imaginary and the moral economy of fair trade foods. Political Geography, 23, 891–915. https://doi.org/10.1016/j.polgeo.2004.05.013 .Goodman, D., DuPuis, E.M., Goodman, M.K. (2012). Alternative food networks: Knowledge, place and politics. Routledge, Oxon, New York. ISBN: 9780203804520.Goodman, D., DuPuis, E. M., & Goodman, M. K. (2013). Engaging alternative food networks: Commentaries and research agendas. International Journal of Sociology of Agriculture and Food, 20, 425–431.Guinot, E. (2008) El paisaje de la Huerta de Valencia. Elementos de interpretación de su morfología espacial de origen medieval. Historia de la Ciudad V. Tradición y progreso, 98–111. Valencia: Icaro-Colegio Territorial de Arquitectos de Valencia-Universidad Politécnica de Valencia.Guthman, J. (2004). Agrarian dreams: The paradox of organic farming in California. University of California Press, Berkeley. ISBN-10: 0520240952.Hubeau, M., Coteur, I., Mondelaers, K., & Marchand, F. (2015). Systeembeschrijving van het Vlaamse Landbouw- en Voedingssysteem: een nulmeting. Merelbeke, Belgie: ILVO.Ilbery, B., & Maye, D. (2005). Alternative (shorter) food supply chains and specialist livestock products in the Scottish - English borders. Environment and Planning, 37, 823–844. https://doi.org/10.1068/a3717 .IPCC (2012). Glossary of terms. In C. B. Field, V. Barros, T. F. Stocker, D. Qin, D. J. Dokken, K. L. Ebi et al. (Eds.), Managing the Risks of Extreme Events and Disasters to Advance Climate Change Adaptation. A Special Report of Working Groups I and II of the Intergovernmental Panel on Climate Change (IPCC), (pp. 555–564). Cambridge: Cambridge University Press.Jarosz, L. (2007). The city in the country: Growing alternative food networks in metropolitan areas. Journal of Rural Studies, 24, 231–244. https://doi.org/10.1016/j.jrurstud.2007.10.002 .Jones, I. (2012). Evaluation of the community food co-operative programme in Wales, BMG research, Welsh Government social research, 22/2012.Kirwan, J., & Maye, D. (2013). Food security framings within the UK and the integration of local food systems. Journal of Rural Studies, 29, 91–100. https://doi.org/10.1016/j.jrurstud.2012.03.002 .Lamine, C. (2015). Sustainability and resilience in Agrifood systems: Reconnecting agriculture, food and the environment. Sociologia Ruralis, 55, 41–61. https://doi.org/10.1111/soru.12061 .Loopstra, R., Reeves, A., McKee, M., & Stuckler, D. (2016). Food insecurity and social protection in Europe: Quasi-natural experiment of Europe’s great recessions 2004–2012. Preventive Medicine, 89, 44–50. https://doi.org/10.1016/j.ypmed.2016.05.010 .MacMillan, T., & Dowler, E. (2012). Just and sustainable? Examining the rhetoric and potential realities of UK food security. Journal of Agricultural and Environmental Ethics, 25, 181–204. https://doi.org/10.1007/s10806-011-9304-8 .Marsden, T., Banks, J., Bristow, G. (2000). Food supply chain approaches: exploring their role in rural development. Sociologia Ruralis, https://doi.org/10.1111/1467-9523.00158Maxwell, S. (1996). Food security: A post-modern perspective. Food Policy, 21, 155–170. https://doi.org/10.1016/0306-9192(95)00074-7 .Mooney, P.H., Hunt, S.A. (2009). Food security: The elaboration of contested claims to a consensus frame. Sociologia Ruralis. https://doi.org/10.1111/j.1549-0831.2009.tb00701.x .Moragues-Faus, A. (2016). Participative action research: Transforming Cardiff’s food system through students’ live projects. Report available at http://foodcardiff.com/wp-content/uploads/2016/10/Report-live-projects-2016-cut-.pdf. . Accessed Sept 2017.Moragues-Faus, A. (2017a). Emancipatory or neoliberal food politics? Exploring the “politics of collectivity” of buying groups in the search for egalitarian food democracies. Antipode, 49, 455–476. https://doi.org/10.1111/anti.12274 .Moragues-Faus, A. (2017b). Problematising justice definitions in public food security debates: Towards global and participative food justices. Geoforum, 84, 95–106. https://doi.org/10.1016/j.geoforum.2017.06.007 .Moragues-Faus, A., & Marsden, T. (2017). The political ecology of food: Carving “spaces of possibility” in a new research agenda. Journal of Rural Studies, 55, 275–288. https://doi.org/10.1016/j.jrurstud.2017.08.016 .Moragues-Faus, A., Sonnino, R., 2012. Embedding quality in the agro-food system: The dynamics and implications of place-making strategies in the olive oil sector of alto Palancia, Spain. Sociologia Ruralis, https://doi.org/10.1111/j.1467-9523.2011.00558.x .Morgan, K., & Sonnino, R. (2010). The urban foodscape: World cities and the new food equation. Cambridge Journal of Regions, Economy and Society, 3, 209–224. https://doi.org/10.1093/cjres/rsq007 .Murdoch, J., & Miele, M. (1999). “Back to nature”: Changing “worlds of production” in the food sector. Sociologia Ruralis, 39, 465–483. https://doi.org/10.1111/1467-9523.00119 .Murdoch, J., Marsden, T., & Banks, J. (2000). Quality, nature, and embeddedness: Some theoretical considerations in the context of the food sector. Economic Geography, 76, 107–125. https://doi.org/10.1111/j.1944-8287.2000.tb00136.x .OECD, FAO, UNCDF (2016). Adopting a territorial approach to food security and nutrition policy. Paris. https://doi.org/10.1787/9789264257108-en .Ortiz-Miranda, D., Moragues-Faus, A.M., 2014. Governing fair trade coffee supply: dynamics and challenges in small farmers’ organizations. Sustainable Development, https://doi.org/10.1002/sd.1570 .Oxfam and Church Action. (2013). Walking the breadline: The scandal of food poverty in 21st-century Britain. http://policy-practice.oxfam.org.uk/publications/walking-the-breadline-the-scandal-of-food-poverty-in-21st-century-britain-292978 . Accessed 19 August 2014.Padel, S., & Foster, C. (2005). Exploring the gap between attitudes and behaviour: Understandingwhy consumers buy or do not buy organic food. British Food Journal, 107, 606–625. https://doi.org/10.1108/00070700510611002 .Radhika Ch., Hemantha U., 2017. Research study on nutrition security and equity in its access in watershed development programmes. Research reports series 107. National Institute of Rural Development & Panchayati Raj. ISBN 978-93-84503-81-9.Renting, H., Marsden, T. K., & Banks, J. (2003). Understanding alternative food networks: Exploring the role of short food supply chains in rural development. Environment and Planning, 35, 393–411. https://doi.org/10.1068/a3510 .Renting, H., Schermer, M., & Rossi, A. (2012). Building food democracy: Exploring civic food networks and newly emerging forms of food citizenship. International Journal of Sociology of Agriculture and Food, 19, 289–307.Romero, J., & Francés, M. (Eds.). (2012). La Huerta de Valencia. Un paisaje cultural con futuro incierto. Valencia: Publicaciones de la Universitat de València.Sage, C. (2003). Social embeddedness and relations of regard: Alternative “good food” networks in south-West Ireland. Journal of Rural Studies, 19, 47–60. https://doi.org/10.1016/S0743-0167(02)00044-X .Sonnino, R., & Marsden, T. (2006). Beyond the divide: Rethinking relationships between alternative and conventional food networks in Europe. Journal of Economic Geography, 6, 181–199. https://doi.org/10.1093/jeg/lbi006 .Sonnino, R., Marsden, T., & Moragues-Faus, A. (2016). Relationalities and convergences in food security narratives: Towards a place-based approach. Transactions of the Institute of British Geographers, 41, 477–489. https://doi.org/10.1111/tran.12137 .Soriano i Piqueras, V. (2015). La huerta de Valencia un paisaje menguante. Amazon. ISBN-13: 978-1512009231.Stanners, D., & Bourdeau, P. (1995). Europe’s environment: The Dobris assessment. Copenhagen: European Environmental Agency.Tregear, A. (2011). Progressing knowledge in alternative and local food networks: Critical reflections and a research agenda. Journal of Rural Studies, 27, 419–430. https://doi.org/10.1016/j.jrurstud.2011.06.003 .Valencia City Council. (2016). Department of Agricultura and Huerta (ongoing review). Pla d’Acció Integral per a la promoció de l’activitat i el territori agrícola municipal. https://hortaipoblesvalencia.org/es/agricultura-y-huerta/ . Accessed Jan 2018.Van Gameren, V., Ruwet, C., & Bauler, T. (2015). Towards a governance of sustainable consumption transitions: How institutional factors influence emerging local food systems in Belgium. Local Environment: The international journal of justice and sustainability, https://doi.org/10.1080/13549839.2013.872090 .Venn, L., Kneafsey, M., Holloway, L., Cox, R., Dowler, E., & Tuomainen, H. (2006). Researching European “alternative” food networks: Some methodological considerations. Area, 38, 248–258. https://doi.org/10.1111/j.1475-4762.2006.00694.x .Vervoort, J., Thornton, P. K., Kristjanson, P., et al. (2014). Challenges to scenario-guided adaptive action on food security under climate change. Global Environmental Change, 28, 383–394. https://doi.org/10.1016/j.gloenvcha.2014.03.001 .Weingartner L. (2005). Paper I. The concept of food and nutrition security. In: Klennert K, editor. Achieving food and nutrition security: Actions to meet the global challenge: A training course reader. Feldafing: German Society for International Cooperation; p. 3–28. ISBN 3-937235 -71-X.Whatmore, S., Stassart, P., & Renting, H. (2003). What’s alternative about alternative food networks? Environment and Planning, 35, 389–391. https://doi.org/10.1068/a3621 .Zwart, T. A., Mathijs, E., Avermaete, T. (2016). Can alternative food networks contribute to a transition towards sustainability in Flanders: Assessing the marketing functions of Voedselteams. Report available at http://ageconsearch.umn.edu/record/245069/files/BioeconWP_2016_04_submitted.pdf . Accessed Sept 2017

Proinflammatory Phenotype and Increased Caveolin-1 in Alveolar Macrophages with Silenced CFTR mRNA

The inflammatory milieu in the respiratory tract in cystic fibrosis (CF) has been linked to the defective expression of the cystic transmembrane regulator (CFTR) in epithelial cells. Alveolar macrophages (AM), important contibutors to inflammatory responses in the lung, also express CFTR. The present study analyzes the phenotype of human AM with silenced CFTR. Expression of CFTR mRNA and the immature form of the CFTR protein decreased 100-fold and 5.2-fold, respectively, in AM transfected with a CFTR specific siRNA (CFTR-siRNA) compared to controls. Reduction of CFTR expression in AM resulted in increased secretion of IL-8, increased phosphorylation of NF-κB, a positive regulator of IL-8 expression, and decreased expression of IκB-α, the inhibitory protein of NF-κB activation. AM with silenced CFTR expression also showed increased apoptosis. We hypothesized that caveolin-1 (Cav1), a membrane protein that is co-localized with CFTR in lipid rafts and that is related to inflammation and apoptosis in macrophages, may be affected by decreased CFTR expression. Messenger RNA and protein levels of Cav1 were increased in AM with silenced CFTR. Expression and transcriptional activity of sterol regulatory element binding protein (SREBP), a negative transcriptional regulator of Cav1, was decreased in AM with silenced CFTR, but total and free cholesterol mass did not change. These findings indicate that silencing of CFTR in human AM results in an inflammatory phenotype and apoptosis, which is associated to SREBP-mediated regulation of Cav1