scholarly journals Organ-Specific Role of MyD88 for Gene Regulation during Polymicrobial Peritonitis

2006 ◽  
Vol 74 (6) ◽  
pp. 3618-3632 ◽  
Author(s):  
Heike Weighardt ◽  
Jörg Mages ◽  
Gabriela Jusek ◽  
Simone Kaiser-Moore ◽  
Roland Lang ◽  
...  

ABSTRACT Sepsis leads to the rapid induction of proinflammatory signaling cascades by activation of the innate immune system through Toll-like receptors (TLR). To characterize the role of TLR signaling through MyD88 for sepsis-induced transcriptional activation, we investigated gene expression during polymicrobial septic peritonitis by microarray analysis. Comparison of gene expression profiles for spleens and livers from septic wild-type and MyD88-deficient mice revealed striking organ-specific differences. Whereas MyD88 deficiency strongly reduced sepsis-induced gene expression in the liver, gene expression in the spleen was largely independent of MyD88, indicating organ-specific transcriptional regulation during polymicrobial sepsis. In addition to genes regulated by MyD88 in an organ-dependent manner, we also identified genes that exhibited an organ-independent influence of MyD88 and mostly encoded cytokines and chemokines. Notably, the expression of interferon (IFN)-regulated genes was markedly increased in septic MyD88-deficient mice compared to that in septic wild-type controls. Expression of IFN-regulated genes was dependent on the adapter protein TRIF. These results suggest that the influence of MyD88 on gene expression during sepsis strongly depends on the organ compartment affected by inflammation and that the lack of MyD88 may lead to disbalance of the expression of IFN-regulated genes.

Genetics ◽  
2001 ◽  
Vol 158 (1) ◽  
pp. 41-64 ◽  
Author(s):  
Justin Courcelle ◽  
Arkady Khodursky ◽  
Brian Peter ◽  
Patrick O Brown ◽  
Philip C Hanawalt

Abstract The SOS response in UV-irradiated Escherichia coli includes the upregulation of several dozen genes that are negatively regulated by the LexA repressor. Using DNA microarrays containing amplified DNA fragments from 95.5% of all open reading frames identified on the E. coli chromosome, we have examined the changes in gene expression following UV exposure in both wild-type cells and lexA1 mutants, which are unable to induce genes under LexA control. We report here the time courses of expression of the genes surrounding the 26 documented lexA-regulated regions on the E. coli chromosome. We observed 17 additional sites that responded in a lexA-dependent manner and a large number of genes that were upregulated in a lexA-independent manner although upregulation in this manner was generally not more than twofold. In addition, several transcripts were either downregulated or degraded following UV irradiation. These newly identified UV-responsive genes are discussed with respect to their possible roles in cellular recovery following exposure to UV irradiation.


Dose-Response ◽  
2021 ◽  
Vol 19 (2) ◽  
pp. 155932582110198
Author(s):  
Mohammed S. Aldughaim ◽  
Mashael R. Al-Anazi ◽  
Marie Fe F. Bohol ◽  
Dilek Colak ◽  
Hani Alothaid ◽  
...  

Cadmium telluride quantum dots (CdTe-QDs) are acquiring great interest in terms of their applications in biomedical sciences. Despite earlier sporadic studies on possible oncogenic roles and anticancer properties of CdTe-QDs, there is limited information regarding the oncogenic potential of CdTe-QDs in cancer progression. Here, we investigated the oncogenic effects of CdTe-QDs on the gene expression profiles of Chang cancer cells. Chang cancer cells were treated with 2 different doses of CdTe-QDs (10 and 25 μg/ml) at different time intervals (6, 12, and 24 h). Functional annotations helped identify the gene expression profile in terms of its biological process, canonical pathways, and gene interaction networks activated. It was found that the gene expression profiles varied in a time and dose-dependent manner. Validation of transcriptional changes of several genes through quantitative PCR showed that several genes upregulated by CdTe-QD exposure were somewhat linked with oncogenesis. CdTe-QD-triggered functional pathways that appear to associate with gene expression, cell proliferation, migration, adhesion, cell-cycle progression, signal transduction, and metabolism. Overall, CdTe-QD exposure led to changes in the gene expression profiles of the Chang cancer cells, highlighting that this nanoparticle can further drive oncogenesis and cancer progression, a finding that indicates the merit of immediate in vivo investigation.


2021 ◽  
Author(s):  
Zheng Wei ◽  
Xiaomei Liu ◽  
Taiming Li ◽  
Xiaofang Li ◽  
Qungang Zhou ◽  
...  

Aim: Adeno-associated virus (AAV) is the most preferred gene therapy vector. The purpose of our research is to compare the infection tropism and gene expression efficiency of vitreous injection of recombinant AAVs (rAAVs) and their capsid mutants in mouse retina. Materials & methods: We packaged wild-type rAAV2/2,6,8,9 and their capsid mutants carrying EGFP expression cassette using insect cells. The gene expression profiles of rAAVs and their mutants in mouse retina were evaluated by optical imaging of retinal tissue flat mount and cryosections. Results & conclusion: The results showed that rAAV2 and rAAV2-Y444F mainly targeted retinal ganglion cell; rAAV8, rAAV8-Y733F, rAAV9 and mutants had obvious EGFP expression in retinal pigment epithelium cells. Compared with the wild-type rAAVs, capsid mutants have an improved transduction efficiency in mouse retina cells.


2019 ◽  
Vol 20 (12) ◽  
pp. 3073 ◽  
Author(s):  
Ana Dienstbier ◽  
Fabian Amman ◽  
Daniel Štipl ◽  
Denisa Petráčková ◽  
Branislav Večerek

Bordetella pertussis is a Gram-negative strictly human pathogen of the respiratory tract and the etiological agent of whooping cough (pertussis). Previously, we have shown that RNA chaperone Hfq is required for virulence of B. pertussis. Furthermore, microarray analysis revealed that a large number of genes are affected by the lack of Hfq. This study represents the first attempt to characterize the Hfq regulon in bacterial pathogen using an integrative omics approach. Gene expression profiles were analyzed by RNA-seq and protein amounts in cell-associated and cell-free fractions were determined by LC-MS/MS technique. Comparative analysis of transcriptomic and proteomic data revealed solid correlation (r2 = 0.4) considering the role of Hfq in post-transcriptional control of gene expression. Importantly, our study confirms and further enlightens the role of Hfq in pathogenicity of B. pertussis as it shows that Δhfq strain displays strongly impaired secretion of substrates of Type III secretion system (T3SS) and substantially reduced resistance to serum killing. On the other hand, significantly increased production of proteins implicated in transport of important metabolites and essential nutrients observed in the mutant seems to compensate for the physiological defect introduced by the deletion of the hfq gene.


2017 ◽  
Vol 5 (0) ◽  
pp. 21-35 ◽  
Author(s):  
Shiori Miura ◽  
Takehiro Himaki ◽  
Junko Takahashi ◽  
Hitoshi Iwahashi

2006 ◽  
Vol 2 ◽  
pp. S552-S552
Author(s):  
Boe-Hyun Kim ◽  
Jae-Il Kim ◽  
Eun-Kyoung Choi ◽  
Richard I. Carp ◽  
Yong-Sun Kim

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