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Human CAR NK Cells: A New Non-viral Method Allowing High Efficient Transfection and Strong Tumor Cell Killing
In conclusion, the method of NK cell transfection described in our present study is highly efficient, does not require expensive dedicated structures necessary for viral transduction and avoids possible risks associated with the use of viral vectors. Importantly, it may be applied to NK cells or NK-92 cell line, greatly improving their anti-tumor activity and providing a new NK cell-based platform for new protocols of adoptive immuno-therapy of cancer. Ethics Statement The Ethical Committee of IRCCS Bambino Gesù Pediatric Hospital approved the study (825/2014). Author Contributions TI designed and performed res...
Source: Frontiers in Immunology - April 29, 2019 Category: Allergy & Immunology Source Type: research

Plant-Derived Alkaloids: The Promising Disease-Modifying Agents for Inflammatory Bowel Disease
Conclusion This paper summarizes the current findings regarding the anti-colitis activity of plant-derived alkaloids and shows how these alkaloids exhibit significant and beneficial effects in alleviating colonic inflammation. These natural alkaloids are not only promising agents for IBD treatment but are also components for developing new wonder drugs. However, the underlying molecular mechanisms or toxicological evaluation of most plant-derived alkaloids still require much scientific research, and their actual efficacies for IBD patients have not been verified well in field research. Thus, further clinical trials to elu...
Source: Frontiers in Pharmacology - April 11, 2019 Category: Drugs & Pharmacology Source Type: research

Antibacterial effect of mesenchymal stem cells against Escherichia coli is mediated by secretion of beta‐defensin‐2 via toll like receptor 4 signaling
This study was done to elucidate the mechanism underlying the antibacterial effects of MSCs. The growth of E. coli in vitro was significantly inhibited only by MSCs or their conditioned medium with bacterial preconditioning, but not by fibroblasts or their conditioned medium. Microarray analysis identified significant up‐regulation of toll like receptors (TLR)‐2 and TLR‐4, and β‐defensin 2 (BD2) in MSCs compared with fibroblasts after E. coli exposure. The increased BD2 level and the in vitro antibacterial effects of MSCs were abolished by specific antagonist or by siRNA‐mediated knockdown of TLR‐4, but not TL...
Source: Cellular Microbiology - September 1, 2015 Category: Microbiology Authors: Dong Kyung Sung, Yun Sil Chang, Se In Sung, Hye Soo Yoo, So Yoon Ahn, Won Soon Park Tags: Research article Source Type: research

JAK1/STAT3 activation directly inhibits IL-12 production in dendritic cells by preventing CDK9/P-TEFb recruitment to the p35 promoter.
Abstract Inhibition of Janus-activated kinase-1 (JAK1) is a promising clinical concept for post-transplant immunosuppression and autoimmunity. However, it also raises concerns regarding possible immunosuppressive side effects. Our study investigates JAK1 signalling in the context of CD40L and bacterially activated human MoDC using siRNA and biological inhibitors. We demonstrate that strong stimuli (e.g. intact E. coli or LPS in addition to IL-1β) induce IL-12p70 via a ROS/RELA/CDK9 pathway that is inhibited by simultaneous JAK1/STAT3 signalling. Transcription is effective if RELA recruits the positive transcripti...
Source: Biochemical Pharmacology - April 27, 2015 Category: Drugs & Pharmacology Authors: Wagner AH, Conzelmann M, Fitzer F, Giese T, Gülow K, Falk CS, Krämer OH, Dietrich S, Hecker M, Luft T Tags: Biochem Pharmacol Source Type: research