Last data update: Jun 11, 2024. (Total: 46992 publications since 2009)
Records 1-7 (of 7 Records) |
Query Trace: Tkach AV [original query] |
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MDSC and TGF-beta are required for facilitation of tumor growth in the lungs of mice exposed to carbon nanotubes
Shvedova AA , Kisin ER , Yanamala N , Tkach AV , Gutkin DW , Star A , Shurin GV , Kagan VE , Shurin MR . Cancer Res 2015 75 (8) 1615-23 During last decades, changes have been observed in the frequency of different histological subtypes of lung cancer - one of the most common causes of morbidity and mortality - with a declining proportion of squamous cell carcinomas and an increasing proportion of adenocarcinomas, particularly in developed countries. This suggests the emergence of new etiological factors and mechanisms including those defining the lung microenvironment promoting tumor growth. Assuming that the lung is the main portal of entry for broadly used nanomaterials and their established pro-inflammatory propensities, we hypothesized that nanomaterials may contribute to changes facilitating tumor growth. Here we report that an acute exposure to single-walled carbon nanotubes (SWCNT) induces recruitment and accumulation of lung-associated myeloid-derived suppressor cells (MDSC) and MDSC-derived production of TGF-beta resulting in up-regulated tumor burden in the lung. The production of TGF-beta by MDSC requires their interaction with both SWCNT and tumor cells. We conclude that pulmonary exposure to SWCNT favors the formation of a niche that supports ingrowth of lung carcinoma in vivo via activation of TGF-beta production by SWCNT-attracted and pre-sensitized MDSC. |
Graphene oxide attenuates Th2-type immune responses, but augments airway remodeling and hyperresponsiveness in a murine model of asthma
Shurin MR , Yanamala N , Kisin ER , Tkach AV , Shurin GV , Murray AR , Leonard HD , Reynolds JS , Gutkin DW , Star A , Fadeel B , Savolainen K , Kagan VE , Shvedova AA . ACS Nano 2014 8 (6) 5585-99 Several lines of evidence indicate that exposure to nanoparticles (NPs) is able to modify airway immune responses, thus facilitating the development of respiratory diseases. Graphene oxide (GO) is a promising carbonaceous nanomaterial with unique physicochemical properties, envisioned for a multitude of medical and industrial applications. In this paper, we determined how exposure to GO modulates the allergic pulmonary response. Using a murine model of ovalbumin (OVA)-induced asthma, we revealed that GO, given at the sensitization stage, augmented airway hyperresponsiveness and airway remodeling in the form of goblet cell hyperplasia and smooth muscle hypertrophy. At the same time, the levels of the cytokines IL-4, IL-5, and IL-13 were reduced in broncho-alveolar lavage (BAL) fluid in GO-exposed mice. Exposure to GO during sensitization with OVA decreased eosinophil accumulation and increased recruitment of macrophages in BAL fluid. In line with the cytokine profiles, sensitization with OVA in the presence of GO stimulated the production of OVA-specific IgG2a and down-regulated the levels of IgE and IgG1. Moreover, exposure to GO increased the macrophage production of the mammalian chitinases, CHI3L1 and AMCase, whose expression is associated with asthma. Finally, molecular modeling has suggested that GO may directly interact with chitinase, affecting AMCase activity, which has been directly proven in our studies. Thus, these data show that GO exposure attenuates Th2 immune response in a model of OVA-induced asthma, but leads to potentiation of airway remodeling and hyperresponsiveness, with the induction of mammalian chitinases. |
Graphene oxide, but not fullerenes, targets immunoproteasomes and suppresses antigen presentation by dendritic cells
Tkach AV , Yanamala N , Stanley S , Shurin MR , Shurin GV , Kisin ER , Murray AR , Pareso S , Khaliullin T , Kotchey GP , Castranova V , Mathur S , Fadeel B , Star A , Kagan VE , Shvedova AA . Small 2013 9 1686-1690 Graphene oxide (GO) and C60- or C60-TRIS fullerenes, internalized by murine dendritic cells (DCs), differently affect their abilities to present antigens to T-cells. While C60-fullerenes stimulate the ovalbumin-specific MHC class I-restricted T-cell response, GO impairs the stimulatory potential of DCs. In contrast to C60-fullerenes, GO decreases the intracellular levels of LMP7 immunoproteasome subunits required for processing of protein antigens. This is important for the development of DC-based vaccines. (Copyright 2013 WILEY-VCH Verlag GmbH Co. KGaA, Weinheim.) |
Carbon nanotubes enhance metastatic growth of lung carcinoma via up-regulation of myeloid-derived suppressor cells
Shvedova AA , Tkach AV , Kisin ER , Khaliullin T , Stanley S , Gutkin DW , Star A , Chen Y , Shurin GV , Kagan VE , Shurin MR . Small 2013 9 1691-1695 Metastatic establishment and growth of Lewis lung carcinoma is promoted by single-walled carbon nanotubes (SWCNT) in C57BL6/J mice. The effect is mediated by increased local and systemic accumulation of myeloid-derived suppressor cells (MDSC), as their depletion abrogated pro-tumor activity in vivo. These data are important for the design of novel theranostics platforms with modules capable of depleting or functionally suppressing MDSC to ensure effective immunosurveillance in the tumor microenvironment. (Copyright 2013 WILEY-VCH Verlag GmbH Co. KGaA, Weinheim.) |
Pulmonary exposure to single-walled carbon nanotubes does not affect the early immune response against Toxoplasma gondii
Swedin L , Arrhigi R , Andersson-Willman B , Murray A , Chen Y , Karlsson MC , Kumlen Georen S , Tkach AV , Shvedova AA , Fadeel B , Barragan A , Scheynius A . Part Fibre Toxicol 2012 9 (1) 16 BACKGROUND: Single-walled carbon nanotubes (SWCNT) trigger pronounced inflammation and fibrosis in the lungs of mice following administration via pharyngeal aspiration or inhalation. Human exposure to SWCNT in an occupational setting may occur in conjunction with infections and this could yield enhanced or suppressed responses to the offending agent. Here, we studied whether the sequential exposure to SWCNT via pharyngeal aspiration and infection of mice with the ubiquitous intracellular parasite Toxoplasma gondii would impact on the immune response of the host against the parasite. METHODS: C57BL/6 mice were pre-exposed by pharyngeal administration of SWCNT (80 + 80 mug/mouse) for two consecutive days followed by intravenous injection with either 1x103 or 1x104 green fluorescence protein and luciferase-expressing T. gondii tachyzoites. The dissemination of T. gondii was monitored by in vivo bioluminescence imaging in real time for 7 days and by plaque formation. The inflammatory response was analysed in bronchoalveolar lavage (BAL) fluid, and by assessment of morphological changes and immune responses in lung and spleen. RESULTS: There were no differences in parasite distribution between mice only inoculated with T. gondii or those mice pre-exposed for 2 days to SWCNT before parasite inoculum. Lung and spleen histology and inflammation markers in BAL fluid reflected the effects of SWCNT exposure and T. gondii injection, respectively. We also noted that CD11c positive dendritic cells but not F4/80 positive macrophages retained SWCNT in the lungs 9 days after pharyngeal aspiration. However, co-localization of T. gondii with CD11c or F4/80 positive cells could not be observed in lungs or spleen. Pre-exposure to SWCNT did not affect the splenocyte response to T. gondii. CONCLUSIONS: Taken together, our data indicate that pre-exposure to SWCNT does not enhance or suppress the early immune response to T. gondii in mice. |
Citrullination of proteins: a common post-translational modification pathway induced by different nanoparticles in vitro and in vivo
Mohamed BM , Verma NK , Davies AM , McGowan A , Staunton KC , Prina-Mello A , Kelleher D , Botting CH , Causey CP , Thompson PR , Pruijn GJ , Kisin ER , Tkach AV , Shvedova AA , Volkov Y . Nanomedicine (London) 2012 7 (8) 1181-95 AIM: Rapidly expanding manufacture and use of nanomaterials emphasize the requirements for thorough assessment of health outcomes associated with novel applications. Post-translational protein modifications catalyzed by Ca(2+)-dependent peptidylargininedeiminases have been shown to trigger immune responses including autoantibody generation, a hallmark of immune complexes deposition in rheumatoid arthritis. Therefore, the aim of the study was to assess if nanoparticles are able to promote protein citrullination. MATERIALS & METHODS: Human A549 and THP-1 cells were exposed to silicon dioxide, carbon black or single-walled carbon nanotubes. C57BL/6 mice were exposed to respirable single-walled carbon nanotubes. Protein citrullination, peptidylargininedeiminases activity and target proteins were evaluated. RESULTS: The studied nanoparticles induced protein citrullination both in cultured human cells and mouse lung tissues. Citrullination occurred via the peptidylargininedeiminase-dependent mechanism. Cytokeratines 7, 8, 18 and plectins were identified as intracellular citrullination targets. CONCLUSION: Nanoparticle exposure facilitated post-translational citrullination of proteins. Original submitted 18 March 2011; Revised submitted 10 Novemeber 2011. |
Direct effects of carbon nanotubes on dendritic cells induce immune suppression upon pulmonary exposure
Tkach AV , Shurin GV , Shurin MR , Kisin ER , Murray AR , Young SH , Star A , Fadeel B , Kagan VE , Shvedova AA . ACS Nano 2011 5 (7) 5755-62 Pharyngeal aspiration of single-walled carbon nanotubes (SWCNTs) caused inflammation, pulmonary damage, and an altered cytokine network in the lung. Local inflammatory response in vivo was accompanied by modified systemic immunity as documented by decreased proliferation of splenic T cells. Preincubation of naive T cells in vitro with SWCNT-treated dendritic cells reduced proliferation of T cells. Our data suggest that in vivo exposure to SWCNT modifies systemic immunity by modulating dendritic cell function. |
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