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RISS 인기검색어
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- 저자 : ( Bernd Heinrich ) (검색결과 3 건)
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( Su Jong Yu ),( Chi Ma ),( Bernd Heinrich ),( Zachary J. Brown ),( Milan Sandhu ),( Qianfei Zhang ),( Qiong Fu ),( David Agdashian ),( Firouzeh Korangy ),( Tim F. Greten ) 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1
Aims: Cytokine-induced killer (CIK) cell-based immunotherapy is effective as adjuvant therapy in early stage hepatocellular car cinoma (HCC), but lacks efficacy in advanced HCC. We inves tigated immune suppressor mechanisms and focused on CIKs and myeloid-derived suppressor cells (MDSCs). Methods: MDSCs were quantified by flow cytometry, PCR, and immunohistochemistry. Cytokines were detected by cytokine array. LDH cytotoxicity assay was performed in the presence or absence of MDSCs to study CIK function against HCC cells in vitro. An FDA approved PDE5 inhibitor, tadalafil, was used to target MDSCs in vitro and in vivo. Two different murine HCC cell lines were tested as subcutaneous and orthotopic tumor models in C57BL/6 and BALB/c mice. Anti-tumor effects of hu man CIK and MDSC were tested in vitro. Results: Adoptive cell transfer of CIK cells into tumor bearing mice induced inflammatory mediators (e.g., CX3CL1, IL-13) in the tumor microenvironment and an increase of tumor infil trating MDSCs leading to impaired anti-tumor activity in two different HCC tumor models. MDSCs efficiently suppressed the cytotoxic activity of CIK cells in vitro. In contrast, treatment with a PDE5 inhibitor reversed MDSC suppressor function via ARG1 and iNOS blockade and systemic treatment with a PDE5 inhibitor prevented MDSC accumulation in the tumor microen vironment upon CIK cell therapy and increased its anti-tumor efficacy. Similar results were seen when human CIK cells were tested in vitro in the presence of CD14+HLA-DR<sup>-/low</sup> MDSCs. Treatment of MDSCs with a PDE5 inhibitor suppressed MDSCs suppressor function and enhanced CIK activity against human HCC cell lines in vitro. Conclusions: Our results suggest that targeting MDSCs is an efficient strategy to enhance the antitumor efficacy of CIK cells for the treatment of patients with HCC.
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Stand-alone ClpG disaggregase confers superior heat tolerance to bacteria
Lee, Changhan,Franke, Kamila B.,Kamal, Shady Mansour,Kim, Hyunhee,Lunsdorf, Heinrich,Jager, Jasmin,Nimtz, Manfred,Trč,ek, Janja,Jansch, Lothar,Bukau, Bernd,Mogk, Axel,Romling, Ute National Academy of Sciences 2018 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF Vol.115 No.2
<P><B>Significance</B></P><P>Severe heat stress causes massive protein loss by aggregation ultimately causing cell death. Cellular survival relies on protein disaggregation mediated by the Hsp70-ClpB (Hsp100) bichaperone system in most bacteria. <I>Pseudomonas aeruginosa</I> additionally codes for two stand-alone ClpG disaggregases, which had been acquired by horizontal gene transfer by the species and most abundant clone C strains, respectively. These ClpG disaggregases largely contribute to the resolution of protein aggregates to confer superior heat tolerance partially replacing the DnaK-ClpB system.</P><P>AAA+ disaggregases solubilize aggregated proteins and confer heat tolerance to cells. Their disaggregation activities crucially depend on partner proteins, which target the AAA+ disaggregases to protein aggregates while concurrently stimulating their ATPase activities. Here, we report on two potent ClpG disaggregase homologs acquired through horizontal gene transfer by the species <I>Pseudomonas aeruginosa</I> and subsequently abundant <I>P. aeruginosa</I> clone C. ClpG exhibits high, stand-alone disaggregation potential without involving any partner cooperation. Specific molecular features, including high basal ATPase activity, a unique aggregate binding domain, and almost exclusive expression in stationary phase distinguish ClpG from other AAA+ disaggregases. Consequently, ClpG largely contributes to heat tolerance of <I>P. aeruginosa</I> primarily in stationary phase and boosts heat resistance 100-fold when expressed in <I>Escherichia coli</I>. This qualifies ClpG as a potential persistence and virulence factor in <I>P. aeruginosa</I>.</P>
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Alrwashdeh, Saad S.,Markotter, Henning,Haussmann, Jan,Hilger, Andre,Klages, Merle,Muller, Bernd R.,Kupsch, Andreas,Riesemeier, Heinrich,Scholta, Joachim,Manke, Ingo Korean Society of Microscopy 2017 Applied microscopy Vol.47 No.3
In this investigation, synchrotron X-ray imaging was used to investigate the water distribution inside newly developed gas diffusion media in polymer electrolyte membrane fuel cells. In-situ radiography was used to reveal the relationship between the structure of the microporous layer (MPL) and the water flow in a newly developed MPL equipped with randomly arranged holes. A strong influence of these holes on the overall water transport was found. This contribution provides a brief overview to some of our recent activities on this research field.
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