Temporal and Dose-Dependent Hepatic Gene Expression Patterns in Mice Provide New Insights into TCDD-Mediated Hepatotoxicity

ABSTRACT To determine if deoxycytidyl-deoxyguanosine oligonucleotides (CpG ODN) can be used effectively as nonspecific inducers of innate immune defenses for preventative or therapeutic interventions in infectious disease models for nonhuman primates, the present study evaluated the response of rhesus monkey peripheral blood mononuclear cells to three different synthetic CpG ODN classes by defining the cytokine gene expression patterns and by characterizing IFN-α/β responses. Depending on the type and dose of CpG ODN used for stimulation, distinct gene expression patterns were induced. CpG ODN class A (CpG-A ODN) and CpG-C ODN, but not CpG-B ODN, were potent inducers of alpha interferon (IFN-α), and this response was due to IFN-α production by TLR9-positive plasmacytoid dendritic cells. Importantly, there was a dose-dependent increase in IFN-α responses to CpG-A ODN but a dose-dependent decrease in IFN-α responses by CpG-B ODN. The most sustained IFN-α response was induced by CpG-A ODN and was associated with a stronger induction of interferon regulatory factor 7 and the induction of several interferon-stimulated genes. In contrast, and independent of the dose, CpG-B ODN were the weakest inducers of IFN-α but the most potent inducers of proinflammatory cytokines. CpG-C ODN induced cytokine gene expression patterns that were intermediate between those of CpG-A and CpG-B ODN. Thus, the different types of CpG ODN induce different post-TLR9 signaling pathways that result in distinct cytokine gene expression patterns. Based on these findings, A and C class CpG ODN, but not B class CpG ODN, may be particularly suited for use as therapeutic or prophylactic antiviral interventions.

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Distinct Hepatic Gene‐Expression Patterns of NAFLD in Patients With Obesity

Hepatology Communications ◽

10.1002/hep4.1789 ◽

2021 ◽

Author(s):

Sonu Subudhi ◽

Hannah K. Drescher ◽

Laura E. Dichtel ◽

Lea M. Bartsch ◽

Raymond T. Chung ◽

...

Keyword(s):

Gene Expression ◽

Expression Patterns ◽

Gene Expression Patterns ◽

Hepatic Gene Expression

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The effects of dietary a‐linolenic acid or eicosapentaenoic acid on hepatic gene expression patterns in C57BL/6J mice when provided at human equivalent doses

The FASEB Journal ◽

10.1096/fasebj.21.5.a729-c ◽

2007 ◽

Vol 21 (5) ◽

Author(s):

Micah Brandon Flynt ◽

Jay Whelan

Keyword(s):

Gene Expression ◽

Eicosapentaenoic Acid ◽

Linolenic Acid ◽

Expression Patterns ◽

Gene Expression Patterns ◽

Hepatic Gene Expression

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Intake of Watermelon and Watermelon Byproducts in Male Mice Fed a Western-Style Obesogenic Diet Alters Hepatic Gene Expression Patterns, as Determined by RNA Sequencing

Current Developments in Nutrition ◽

10.1093/cdn/nzaa122 ◽

2020 ◽

Vol 4 (8) ◽

Author(s):

Mariana Buranelo Egea ◽

Gavin Pierce ◽

Alexandra R Becraft ◽

Marlena Sturm ◽

Wesley Yu ◽

...

Keyword(s):

Gene Expression ◽

Transcription Factors ◽

Rna Sequencing ◽

Expression Patterns ◽

Gene Expression Patterns ◽

Control Group ◽

Peroxisome Proliferator ◽

Hepatic Gene Expression ◽

Peroxisome Proliferator Activated Receptor ◽

Expression Levels

ABSTRACT Background Consumption of watermelon has been associated with beneficial effects on metabolism, including reductions in systolic blood pressure, improved fasting blood glucose levels, and changes in hepatic metabolite accumulation. Objectives In the present study, we investigated the impact of consumption of watermelon flesh (WF), watermelon rind (WR), and watermelon skin (WS) on hepatic gene expression patterns in an obesogenic mouse model. Methods Hepatic RNA was isolated and RNA sequencing was performed following a 10-week feeding trial during which C57BL/6 J mice were provided either a low-fat diet (LF), high-fat diet (HF; controls), or HF plus either WS, WR, or WF. Bioinformatic approaches were used to determine changes in the canonical pathways and gene expression levels for lipid- and xenobiotic-regulating nuclear hormone receptors and other related transcription factors, including the aryl hydrocarbon receptor (AhR), constitutive androstane receptor (CAR), farnesyl X receptor, peroxisome proliferator–activated receptor alpha (PPARα), peroxisome proliferator–activated receptor gamma, liver X receptor, pregnane X receptor, and nuclear factor erythroid 2–related factor 2. Results There were 9394 genes that had unchanged expression levels between all 5 diet groups, and 247, 58, and 34 genes were uniquely expressed in the WF, WR, and WS groups, respectively. The relative levels of mRNAs regulated by AhR, CAR, and PPARα were upregulated in mice in the WF group, as compared to the HF control mice; in comparison, mRNAs regulated mainly by CAR were upregulated in mice in the WR and WS groups, compared to those in the HF control group. Conclusions At modest levels of intake reflective of typical human consumption, mice in the WF, WS, and WR groups exhibited hepatic gene expression profiles that were altered when compared to mice in the HF control group. Several of these changes involve genes regulated by ligand-responsive transcription factors implicated in xenobiotic and lipid metabolisms, suggesting that the modulation of these transcription factors occurred in response to the consumption of WS, WR, and WF. Some of these changes are likely due to nuclear hormone receptor–mediated changes involved in lipid and xenobiotic metabolisms.

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