ESTROGENIC COMPOUNDS SUPPRESSED INTERFERON-GAMMA PRODUCTION IN MOUSE SPLENOCYTES THROUGH DIRECT CELL-CELL INTERACTION

Author(s):  
MAKO NAKAYA ◽  
MASAO YAMASAKI ◽  
YOSHIYUKI MIYAZAKI ◽  
Hirofumi Tachibana ◽  
KOJI YAMADA
Materials ◽  
2018 ◽  
Vol 12 (1) ◽  
pp. 31 ◽  
Author(s):  
Xiuhui Wang ◽  
Jingchao Li ◽  
Naoki Kawazoe ◽  
Guoping Chen

Nanoparticle-mediated photothermal therapy has been widely studied for cancer treatment. It is important to disclose how photothermally ablated tumor cells trigger immune responses. In this study, bovine serum albumin (BSA)-coated gold nanorods (BSA-coated AuNRs) were prepared and used for photothermal ablation of breast tumor cells. The BSA-coated AuNRs showed high photothermal conversion efficiency and good photothermal ablation effect towards tumor cells. The ablated tumor cells were co-cultured with immature dendritic cells (DCs) through a direct cell contacting model and diffusion model to confirm the stimulatory effects of cell–cell interaction and soluble factors released from ablated tumor cells. The results indicated that photothermally ablated tumor cells induced immune-stimulatory responses of DCs through both cell–cell interaction and soluble factors. The results should be useful for synergistic photothermal-immunotherapy of primary and metastatic cancer.


Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1406-1406
Author(s):  
Wolfgang Wagner ◽  
Frederik Wein ◽  
Anke Diehlmann ◽  
Rainer Saffrich ◽  
Patrick Wuchter ◽  
...  

Abstract Self renewal and differentiation of hematopoietic progenitor cells (HPC) are regulated by the microenvironment of the bone marrow. As an in vitro model system, mesenchymal stromal cells (MSC) provide a supportive cellular microenvironment for maintaining primitive function of HPC. It has been postulated that direct cell-cell interaction is crucial for maintenance of “stemness”. Human HPC were co-cultured with MSC from human bone marrow and subsequently separated into an adherent and a non-adherent fraction. HPC subsets with higher self-renewing capacity demonstrated significantly higher adhesion to MSC (CD34+vs. CD34−, CD34+/CD38−vs. CD34+/CD38+, slow dividing fraction vs. fast dividing fraction). Long-term culture-initiating cell (LTC-IC) frequency was higher in the adherent fraction than in the non-adherent fraction of CD34+ cells. Microarray analysis (Affymetrix, U133_Plus_2.0) revealed that differentially expressed genes coding for adhesion proteins were highly up-regulated in the adherent fraction of CD34+ cells. These genes included VCAM1, connexin 43 and cadherin-11. Furthermore, we have compared the supportive potential of different feeder layer preparations. Human MSC were isolated from bone marrow (BM), from adipose tissue (AT) and umbilical cord blood (CB). The ability to maintain LTC-IC and a primitive CD34+CD38− immunophenotype was significantly higher for MSC derived from BM and CB compared to those from AT. These results were in line with higher adhesion of HPC to BM-MSC and CB-MSC in comparison to AT-MSC. Analysis of the cytokine production of MSC preparations by antibody arrays, ELISA and by a cytometric bead array showed that albeit there were significant differences in the chemokine secretion profiles of the aforementioned MSC preparations, there was no relationship to their potentials in maintaining primitive function of HPC. Global gene expression profiles of MSC preparations showed that adhesion proteins including N-cadherin, cadherin-11, VCAM1, NCAM1 and integrins were highly expressed in MSC preparations derived from BM and CB. Western blot analysis confirmed higher protein expression of N-cadherin and cadherin-11 in BM-MSC compared to AT-MSC and CB-MSC. Fluorescent microscopic analysis revealed that N-cadherin is located at the cell-cell contacts between HPC and MSC. Expression of N-cadherin or cadherin-11 was efficiently knocked down in MSC feeder layer using siRNA. This effect was verified by Western blot analysis and it lasted for up to seven days. Adhesion of HPC was significantly reduced on MSC that have been treated by siRNAs for N-cadherin and cadherin-11 whereas siRNA for MAPK did not affect cell-cell interaction. Similarly, a blocking functional antibody for N-cadherin reduced significantly the adhesion of HPC to MSC. MSC provide a microenvironment which supports the maintenance of primitive function of HPC. Our results indicated that direct cell-cell interaction mediated by N-cadherin and cadherin-11 plays a central role in this interaction of HPC with their cellular microenvironment.


Stroke ◽  
2020 ◽  
Vol 51 (4) ◽  
pp. 1279-1289 ◽  
Author(s):  
Akie Kikuchi-Taura ◽  
Yuka Okinaka ◽  
Yukiko Takeuchi ◽  
Yuko Ogawa ◽  
Mitsuyo Maeda ◽  
...  

Background and Purpose— Bone marrow mononuclear cells (BM-MNCs) are a rich source of hematopoietic stem cells and have been widely used in experimental therapies for patients with ischemic diseases. Activation of angiogenesis is believed to be one of major BM-MNC mode of actions, but the essential mechanism by which BM-MNCs activate angiogenesis have hitherto been elusive. The objective of this study is to reveal the mechanism how BM-MNCs activate angiogenesis. Methods— We have evaluated the effect of direct cell-cell interaction between BM-MNC and endothelial cell on uptake of VEGF (vascular endothelial growth factor) into endothelial cells in vitro. Cerebral ischemia model was used to evaluate the effects of direct cell-cell interaction with transplanted BM-MNC on endothelial cell at ischemic tissue. Results— The uptake of VEGF into endothelial cells was increased by BM-MNC, while being inhibited by blockading the gap junction. Low-molecular-weight substance was transferred from BM-MNC into endothelial cells via gap junctions in vivo, followed by increased expression of hypoxia-inducible factor-1α and suppression of autophagy in endothelial cells. The concentration of glucose in BM-MNC cytoplasm was significantly higher than in endothelial cells, and transfer of glucose homologue from BM-MNC to endothelial cells was observed. Conclusions— Our findings demonstrated cell-cell interaction via gap junction is the prominent pathway for activation of angiogenesis at endothelial cells after ischemia and provided novel paradigm that energy source supply by stem cell to injured cell is one of the therapeutic mechanisms of cell-based therapy. Visual Overview— An online visual overview is available for this article.


2012 ◽  
Vol 5 (220) ◽  
pp. ra31-ra31 ◽  
Author(s):  
M. Matsuda ◽  
M. Koga ◽  
E. Nishida ◽  
M. Ebisuya

2003 ◽  
Vol 125 (6) ◽  
pp. 1470-1479 ◽  
Author(s):  
Shinya Fukuhara ◽  
Shinji Tomita ◽  
Seiji Yamashiro ◽  
Takayuki Morisaki ◽  
Chikao Yutani ◽  
...  

2019 ◽  
Vol 63 (8) ◽  
Author(s):  
Jun-ichi Wachino ◽  
Wanchun Jin ◽  
Kouji Kimura ◽  
Yoshichika Arakawa

ABSTRACT The spread of antimicrobial resistance genes (ARGs) among Gram-negative pathogens, including Acinetobacter baumannii, is primarily mediated by transferable plasmids; however, ARGs are frequently integrated into its chromosome. How ARG gets horizontally incorporated into the chromosome of A. baumannii, and whether it functions as a cause for further spread of ARG, remains unknown. Here, we demonstrated intercellular prophage-mediated transfer of chromosomal ARGs without direct cell-cell interaction in A. baumannii. We prepared ARG-harboring extracellular DNA (eDNA) components from the culture supernatant of a multidrug-resistant (MDR) A. baumannii NU-60 strain and exposed an antimicrobial-susceptible (AS) A. baumannii ATCC 17978 strain to the eDNA components. The antimicrobial-resistant (AR) A. baumannii ATCC 17978 derivatives appeared to acquire various ARGs, originating from dispersed loci of the MDR A. baumannii chromosome, along with their surrounding regions, by homologous recombination, with the ARGs including armA (aminoglycoside resistance), blaTEM-1 (β-lactam resistance), tet(B) (tetracycline resistance), and gyrA-81L (nalidixic acid resistance) genes. Notably, the eDNAs conferring antimicrobial resistance were enveloped in specific capsid proteins consisting of phage particles, thereby protecting the eDNAs from detergent and DNase treatments. The phages containing ARGs were likely released into the extracellular space from MDR A. baumannii, thereby transducing ARGs into AS A. baumannii, resulting in the acquisition of AR properties by the recipient. We concluded that the generalized transduction, in which phages were capable of carrying random pieces of A. baumannii genomic DNAs, enabled efficacious intercellular transfer of chromosomal ARGs between A. baumannii strains without direct cell-cell interaction.


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