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" Assessment of therapeutic effects of IL_13/ IL-17 A/F combined blockade on the pulmonary ypertension induced by air polution "
/نفیسه اسماعیل
; Marjan Gharagozloo, Abbas Rezaei, Gbariele Grunig
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Isfahan University of Medical Sciences
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| Document Type
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Latin Dissertation
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| Language of Document
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English
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| Record Number
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103300
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| Doc. No
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T14643
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WG,340,E76a,2014
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| Main Entry
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Esmaeel, Nafiseh
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| Title & Author
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Assessment of therapeutic effects of IL_13/ IL-17 A/F combined blockade on the pulmonary ypertension induced by air polution/نفیسه اسماعیل
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| College
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Schools, Medicine
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| Date
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, 2014
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| Degree
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Immunology, PhD
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90 p.: tab
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| Abstract
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The role of altered immunity and inflammation has been increasingly recognized in various types of pulmonary hypertension (PH) and infiltraion of inflammatory cells, including macrophages, T and B lymphocytes and dendritic cells have shownin pulmonary pervascular spaces and around the plexiform lesions in PAH. pulmonary arterial hypertension (PAH) dramatically reduces the quality of life, life-expectancy and sometimes may forgotten condition which exacerbated by air pollutants. studies demonstrated the CD4+T cells, the IL-4 induced Th2 response, endogenous IL-13 and the IL-17A/F induced Th17 response are important components of the mechanism that causes antigen induced severe pulmonary arterial muscularization and hypertension. on the other hand, impaired expression and function of bone morpogenetic protein receptor gene (BMPR2) is known as a major susceptibility factor for PAH. while several micro RNA (miRNA) that target BMPR2 have been recently shown to be critical components of the pathogenesis of pulmonary hypertension. our study was proposed to further understand the immune response mechanism with focus on the effects of long- term blockade of two arms of immune response(Th2 and Th17), and to understand how the immune response affects expression of microRNAs. which affect BMPR2 gene expression. we used a mouse model of experimental PAH that were induced by antigen (OVA) and urban particulate matters (PM2.5) in which IL-17A/F were co-blockade. to examine the effect of IL-17A/F and IL-13 blockade on PAH right ventricular pressure was measured. inflammatory cells and activation of dendritic cells were assessed in bronchoalveolar lavage(BAL). Th2 and Th17 intracellular cytokines were assessed in lung lymph nodes by flow cytmetry. also BMPR2 , mir-135a and mir-375 gene expression in lung were identified by quantitative reverse transcription PCR. the number of neutrophils and eosinophils were significantly incresed in OVA-PM primed mice compared with saline exposed controland in spite of eosinophils, the mumber of neutrophils in the BALs were significantly reduced after blockage of IL-17A/F and IL-13 also expression of costimulatory molecules (MHCII, CD86) and Th2, Th17 cells count were significantly decreased after blockage of IL-17A/F and IL-13. we found surprisingly high expression of mir135a and low expression of BMPR2. in addition our data clearly showed that the up-regulation of mir135a and down regulation of BMPR2 in response to antigen and PM was not restored to baseline levels following blockade of IL-13 and IL-17A/F. for the first time we showed the simnificance of a mixed immune reponse in a pulmonary hypertension model of mice exposed to antigen (OVA) and ambient particulate matter (PM2.5). this study has clarified hierarchies and networks of inflammatory mediators recognized for their significant roles in clinical pulmonary hypertension. our study is providing a mechanistic approach to miRNa implication in the etiology of PAh and revealed a potent pro-inflammatory role for miRNAs in implication in the etiology of PAH and revealed a otent pro-inflammatory role for miRNAs in pulmonary hypertension..
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| Descriptor
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1. Pulmonary arterial hypertension
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Pulmonary arterial hypertension
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Air Pollution
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Gharagozloo, Marjan, Supervisor
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Rezaei, Abbas, Supervisor
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Grunig, gbariele, Supervisor
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| Translated Title Supplied by Cataloguer
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بررسی اثر درمانی آنتی بادیهای ضد سایتوکاینهای IL-13 و IL-17 A/F بر افزایش فشار خون شریان ریوی (PAH) در مدل موشی ایجاد شده با آلاینده های شهری
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