کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8552701 | 1562269 | 2018 | 44 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Benzo(a)pyrene attenuates the pattern-recognition-receptor induced proinflammatory phenotype of murine macrophages by inducing IL-10 expression in an aryl hydrocarbon receptor-dependent manner
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کلمات کلیدی
BMDCsBAPiNOSRPMITCDDAPCGPCRPAMPPRRMHC-IICCL1ARNTNF-κBTregSIRSM-CSFXRETh1FcγRIPAI-2CYP 450T helper 1 cellBone-marrow derived dendritic cellsPlasminogen activator inhibitor 2FITCPBSMFIHEPESAHRFBSmRNA2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid - 2- [4- (2-hydroxyethyl) piperazin-1-yl] ethanesulfonic acid2,3,7,8-Tetrachlorodibenzo-p-dioxin - 2،3،7،8-تترا کلریدیبنزوپتوفان دیوکسینBMMs - BMM هاDMSO - DMSOfluoresceinisothiocyanate - fluoresceinosothiocyanateG-protein coupled receptor - G-پروتئین همراه گیرندهinducible NO synthase - NO سنتاز القاء شدهStat1 - sTAT1antigen-presenting cell - آنتیژن ارائه سلولpathogen-associated molecular pattern - الگوی مولکولی وابسته به پاتوژنinterleukin - اینترلوکینBenzo(a)pyrene - بنزو (a) پیرنهBenzo(a)pyrene (BaP) - بنزو (a) پیرنه (BaP)ELISA - تست الیزاEnzyme-linked immunosorbent assay - تست الیزاImmunomodulation - تنظیم ایمنی tumor necrosis factor α - تومور نکروز عامل αcluster of differentiation - خوشه تمایزDimethyl sulfoxide - دیمتیل سولفواکسیدmessenger ribonucleic acid - رسوب ریبونوکلئیک اسیدfetal bovine serum - سرم جنین گاوRegulatory T cell - سلول T تنظیم کنندهDendritic cell - سلول دندریتیکNatural killer cell - سلول قاتل طبیعیSystemic inflammatory response syndrome - سندرم پاسخ سیستماتیک التهابیCytochrome P450 - سیتوکروم پی۴۵۰xenobiotic response element - عنصر واکنش زنجبیلTNF-α - فاکتور نکروز توموری آلفاNuclear factor-kappa B - فاکتور هسته ای-کاپا BAhR nuclear translocator - فرستنده هسته ای AhRRoswell Park Memorial Institute - مؤسسه یادبود پارک RoswellMacrophage - ماکروفاژ macrophage colony-stimulating factor - ماکروفاژ عامل کلونی تحریک کنندهBone-Marrow Derived Macrophages - ماکروفاژ های استخوانی-مغز استخوانsignal transducer and activator of transcription 1 - مبدل سیگنال و فعال کننده رونویسی 1Phosphate-buffered saline - محلول نمک فسفات با خاصیت بافریmean fluorescence intensity - میانگین شدت فلورسانسwild-type - نوع وحشیNitric oxide - نیتریک اکسیدAntibody - پادتَن یا آنتیبادیoptical density - چگالی نوریMajor histocompatibility complex class II - کلاس پیچیده بافتی عمده IIaryl hydrocarbon receptor - گیرنده آرویل هیدروکربنpattern recognition receptor - گیرنده شناسایی الگوAryl hydrocarbon receptor (AhR) - گیرنده هیدروکربن آریل (AhR)
موضوعات مرتبط
علوم زیستی و بیوفناوری
علوم محیط زیست
بهداشت، سم شناسی و جهش زایی
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چکیده انگلیسی
Polycyclic aromatic hydrocarbons such as benzo(a)pyrene (BaP) are environmental contaminants known to be immunosuppressive. Most effects of BaP towards immune cells are thought to be mediated through activation of the aryl hydrocarbon receptor (AhR). The AhR is a ligand-activated transcription factor, which plays a critical modulatory role in various cells during immune response. Macrophages are key players in innate immunity against intracellular bacteria and are discussed to be a target of AhR-mediated immune regulation. However, so far there is only incomplete knowledge about the effects of BaP on activated macrophages and whether these effects are AhR-dependent in each case. Using murine bone marrow-derived macrophages (BMMs) stimulated with heat-killed salmonellae as a source of different pathogen-associated molecular patterns (PAMPs) for stimulation of different pattern recognition receptors (PRRs) as an in-vitro model, we studied the immunomodulatory effects of low-dose BaP exposure. PRR-activated BMMs produced nitric oxide (NO) and a spectrum of proinflammatory cytokines, i.e. tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and IL-12 but also the anti-inflammatory cytokine IL-10. While BaP exposure suppressed the production of proinflammatory cytokines, the secretion of IL-10 was augmented. Moreover, BaP exposure increased the expression of major histocompatibility complex class II (MHC-II), CD14, Fcγ receptor I (FcγRI/CD64), or CD86, enhanced NO production and phagocytosis what may be beneficial for phagocytosis and killing of microbial pathogens. Of note, without PRR activation low-dose BaP exposure has little influence on the macrophage phenotype. BMMs from AhR-deficient (Ahrâ/â) mice were widely refractory to BaP-induced modulation of cytokine production, surface marker expression, and functional properties in response to PAMPs stimulation, indicating that these effects are dependent on AhR. In summary, these data suggest that induction of AhR-mediated signalling pathways by BaP may attenuate the proinflammatory phenotype of PRR-activated BMMs, while activating IL-10-mediated anti-inflammatory properties but also enhancing uptake and killing of pathogens as well as antigen presentation. Together these features imply a favourable role of BaP exposure for macrophage functions in an ongoing immune response. However, the strong induction of IL-10 may lead to defective pathogen clearance and subsequently to chronic persistent infection. This concept suggests an inhibitory rather than a supporting influence of environmental BaP on immunity to infection or cancer and also emphasises the important regulatory role of AhR in immunity and inflammation.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology - Volume 409, 1 November 2018, Pages 80-90
Journal: Toxicology - Volume 409, 1 November 2018, Pages 80-90
نویسندگان
Christiane Fueldner, Janine Kohlschmidt, Sina Riemschneider, Felix Schulze, Katharina Zoldan, Charlotte Esser, Sunna Hauschildt, Jörg Lehmann,