Hepatocyte-specific inhibitor-of-kappaB-kinase deletion triggers the innate immune response and promotes earlier cell proliferation during liver regeneration

Hepatology ◽  
2008 ◽  
Vol 47 (6) ◽  
pp. 2036-2050 ◽  
Author(s):  
Yann Malato ◽  
Leif E. Sander ◽  
Christian Liedtke ◽  
Malika Al-Masaoudi ◽  
Frank Tacke ◽  
...  
2007 ◽  
Vol 22 (s1) ◽  
pp. S57-S58 ◽  
Author(s):  
Yuji Iimuro ◽  
Ekihiro Seki ◽  
Gakuhei Son ◽  
Hiroko Tsutsui ◽  
Kenji Nakanishi ◽  
...  

2018 ◽  
Author(s):  
Kyle Spivack ◽  
Christine Muzzelo ◽  
Christopher Neely ◽  
Julia Vanzelli ◽  
Evan Kurt ◽  
...  

AbstractForeign molecules like plasmid DNA trigger a complex and potent innate immune response comprised of highly redundant signal transduction cascades that result in the activation of transcription factors and the production of inflammatory cytokines. Unfortunately, this defense mechanism can hinder gene therapy by inhibiting transgene expression. The goal of this study was to increase transgene expression by inhibiting key components of the innate immune response (β-catenin, NF-κB/AP1, TBK1, TLR9, and p38 MAPK) with small molecule inhibitors (iCRT-14, curcumin, BX-795, E6446, and VX-702 respectively). The effects of each drug on transgene (luciferase) expression, inflammatory cytokine (IL-6) levels, and cell viability were quantified in prostate (PC3), breast (MCF-7), and murine bladder (MB49) cancer cell lines. The β-catenin inhibitor iCRT-14 (1 μM) provided the highest enhancement of 35.5 ± 19-fold in MCF-7 cells, while the other inhibitors increased transgene expression at a more modest level (2-9 fold). The optimal concentrations of iCRT-14, curcumin, and VX-702 showed no significant effect on cell proliferation; however, optimal concentrations of BX-795 and E6446 did significantly reduce cell proliferation. Nonetheless, inhibition of the innate immune response by iCRT-14 and curcumin was confirmed by a concomitant decrease in IL-6 production in PC3 cells. These results demonstrate that these inhibitors can improve gene therapy by preventing an inflammatory innate immune response.


2015 ◽  
Vol 29 (3) ◽  
pp. 119-129 ◽  
Author(s):  
Richard J. Stevenson ◽  
Deborah Hodgson ◽  
Megan J. Oaten ◽  
Luba Sominsky ◽  
Mehmet Mahmut ◽  
...  

Abstract. Both disgust and disease-related images appear able to induce an innate immune response but it is unclear whether these effects are independent or rely upon a common shared factor (e.g., disgust or disease-related cognitions). In this study we directly compared these two inductions using specifically generated sets of images. One set was disease-related but evoked little disgust, while the other set was disgust evoking but with less disease-relatedness. These two image sets were then compared to a third set, a negative control condition. Using a wholly within-subject design, participants viewed one image set per week, and provided saliva samples, before and after each viewing occasion, which were later analyzed for innate immune markers. We found that both the disease related and disgust images, relative to the negative control images, were not able to generate an innate immune response. However, secondary analyses revealed innate immune responses in participants with greater propensity to feel disgust following exposure to disease-related and disgusting images. These findings suggest that disgust images relatively free of disease-related themes, and disease-related images relatively free of disgust may be suboptimal cues for generating an innate immune response. Not only may this explain why disgust propensity mediates these effects, it may also imply a common pathway.


Pneumologie ◽  
2013 ◽  
Vol 67 (S 01) ◽  
Author(s):  
P Pfeifer ◽  
M Voss ◽  
B Wonnenberg ◽  
M Bischoff ◽  
F Langer ◽  
...  

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