scholarly journals Acute sleep fragmentation does not alter pro-inflammatory cytokine gene expression in brain or peripheral tissues of leptin-deficient mice

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e4423 ◽  
Author(s):  
Jennifer E. Dumaine ◽  
Noah T. Ashley
Keyword(s):  
Gene Expression ◽  
Prefrontal Cortex ◽  
Inflammatory Cytokine ◽  
Cytokine Gene Expression ◽  
Cytokine Gene ◽  
Wild Type ◽  
Peripheral Tissues ◽  
Tnf Α ◽  
Deficient Mice ◽  
Tgf Β1

Obesity and sleep fragmentation (SF) are often co-occurring pro-inflammatory conditions in patients with obstructive sleep apnea. Leptin is a peptide hormone produced by adipocytes that has anorexigenic effects upon appetite while regulating immunity. The role of leptin in mediating inflammatory responses to SF is incompletely understood. Male C57BL/6j (lean) and ob/ob mice (leptin-deficient mice exhibiting obese phenotype) were subjected to SF or control conditions for 24 h using an automated SF chamber. Trunk blood and tissue samples from the periphery (liver, spleen, fat, and heart) and brain (hypothalamus, prefrontal cortex, and hippocampus) were collected. Quantitative PCR was used to determine relative cytokine gene expression of pro-inflammatory (IL-1β, TNF-α) and anti-inflammatory (TGF-β1) cytokines. Enzyme-linked immunosorbent assay (ELISA) was used to determine serum corticosterone concentration. Ob/ob mice exhibited elevated cytokine gene expression in liver (TNF-α, TGF-β1), heart (TGF-β1), fat (TNF-α), and brain (hippocampus, hypothalamus, prefrontal cortex: IL-1β, TNF-α) compared with wild-type mice. Conversely, leptin deficiency decreased pro-inflammatory cytokine gene expression in heart (IL-1β, TNF-α). SF significantly increased IL-1β and TNF-α gene expression in fat and TGF-β1 expression in spleen relative to controls, but only in wild-type mice. SF increased basal serum corticosterone regardless of genotype. Taken together, these findings suggest that leptin deficiency affects cytokine gene expression differently in the brain compared to peripheral tissues with minimal interaction from acute SF.

scholarly journals Acute sleep fragmentation induces tissue-specific changes in cytokine gene expression and increases serum corticosterone concentration

2015 ◽  
Vol 308 (12) ◽  
pp. R1062-R1069 ◽  
Author(s):  
Jennifer E. Dumaine ◽  
Noah T. Ashley
Keyword(s):  
Gene Expression ◽  
Stress Hormones ◽  
Sleep Fragmentation ◽  
Cytokine Gene Expression ◽  
Cytokine Gene ◽  
Corticosterone Concentration ◽  
Serum Corticosterone ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Tgf Β1

Sleep deprivation induces acute inflammation and increased glucocorticosteroids in vertebrates, but effects from fragmented, or intermittent, sleep are poorly understood. Considering the latter is more representative of sleep apnea in humans, we investigated changes in proinflammatory (IL-1β, TNF-α) and anti-inflammatory (TGF-β1) cytokine gene expression in the periphery (liver, spleen, fat, and heart) and brain (hypothalamus, prefrontal cortex, and hippocampus) of a murine model exposed to varying intensities of sleep fragmentation (SF). Additionally, serum corticosterone was assessed. Sleep was disrupted in male C57BL/6J mice using an automated sleep fragmentation chamber that moves a sweeping bar at specified intervals (Lafayette Industries). Mice were exposed to bar sweeps every 20 s (high sleep fragmentation, HSF), 120 s (low sleep fragmentation, LSF), or the bar remained stationary (control). Trunk blood and tissue samples were collected after 24 h of SF. We predicted that HSF mice would exhibit increased proinflammatory expression, decreased anti-inflammatory expression, and elevated stress hormones in relation to LSF and controls. SF significantly elevated IL-1β gene expression in adipose tissue, heart (HSF only), and hypothalamus (LSF only) relative to controls. SF did not increase TNF-α expression in any of the tissues measured. HSF increased TGF-β1 expression in the hypothalamus and hippocampus relative to other groups. Serum corticosterone concentration was significantly different among groups, with HSF mice exhibiting the highest, LSF intermediate, and controls with the lowest concentration. This indicates that 24 h of SF is a potent inducer of inflammation and stress hormones in the periphery, but leads to upregulation of anti-inflammatory cytokines in the brain.

scholarly journals Inflammation modulates regeneration in the acute or chronically damaged zebrafish retina

2021 ◽  
Author(s):  
Maria Iribarne ◽  
David Hyde
Keyword(s):  
Gene Expression ◽  
Inflammatory Cytokine ◽  
Gold Rush ◽  
Cytokine Gene Expression ◽  
Retinal Damage ◽  
Cytokine Gene ◽  
Reactive Microglia ◽  
Cytokine Genes ◽  
Tnf Α ◽  
Anti Inflammatory

Unlike mammals, zebrafish regenerate in response to retinal damage. Because microglia are activated by retinal damage, we investigated their role during regeneration following acute or chronic damage. At three weeks-post-fertilization (wpf), fish exhibiting NMDA-induced acute damage or cone photoreceptor-specific chronic degeneration, the gold rush (gosh) mutant, displayed reactive microglia and Müller glia proliferation. Retinas treated to inhibit the immune response lacked reactive microglia and possessed fewer PCNA-positive cells, while LPS treatment increased microglia and PCNA-labeled cells. NMDA-injured retinas upregulated the expression of il-1β and tnf-α pro-inflammatory cytokine genes, followed by increased expression of il-10 and arg1 anti-inflammatory/remodeling cytokine genes. An early and transiently TNF-α pro-inflammatory microglia population was identified in the NMDA-damaged retina. In contrast, gosh mutant retinas exhibited a mild increase of pro-inflammatory cytokine gene expression concurrently with a greater increased in anti-inflammatory/remodeling cytokine gene expression. Few TNF-α pro-inflammatory microglia were observed in the gosh retina. How inflammation regulates regeneration in zebrafish would provide important clues towards improving the therapeutic strategies for repairing injured mammalian tissues.

scholarly journals Rice Bran Protein Hydrolysates Improve Insulin Resistance and Decrease Pro-inflammatory Cytokine Gene Expression in Rats Fed a High Carbohydrate-High Fat Diet

Nutrients ◽  
2015 ◽  
Vol 7 (8) ◽  
pp. 6313-6329 ◽  
Author(s):  
Kampeebhorn Boonloh ◽  
Veerapol Kukongviriyapan ◽  
Bunkerd Kongyingyoes ◽  
Upa Kukongviriyapan ◽  
Supawan Thawornchinsombut ◽  
...  
Keyword(s):  
Gene Expression ◽  
Insulin Resistance ◽  
Rice Bran ◽  
High Fat Diet ◽  
Inflammatory Cytokine ◽  
Cytokine Gene Expression ◽  
Cytokine Gene ◽  
High Fat ◽  
High Carbohydrate ◽  
Improve Insulin Resistance

scholarly journals Febrile-range temperature modifies cytokine gene expression in LPS-stimulated macrophages by differentially modifying NF-κB recruitment to cytokine gene promoters

2010 ◽  
Vol 298 (1) ◽  
pp. C171-C181 ◽  
Author(s):  
Zachary A. Cooper ◽  
Arundhati Ghosh ◽  
Aditi Gupta ◽  
Tapan Maity ◽  
Ivor J. Benjamin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Receptor Activation ◽  
Cytokine Gene Expression ◽  
Raw 264.7 Cells ◽  
Raw 264.7 ◽  
Heat Shock Factor 1 ◽  
Gene Promoters ◽  
Cytokine Gene ◽  
Tnf Α

We previously showed that exposure to febrile-range temperatures (FRT, 39.5–40°C) reduces LPS-induced TNF-α expression, in part through the direct interaction of heat shock factor-1 (HSF1) with the TNF-α gene promoter. However, it is not known whether exposure to FRT also modifies more proximal LPS-induced signaling events. Using HSF1-null mice, we confirmed that HSF1 is required for FRT-induced repression of TNF-α in vitro by LPS-stimulated bone marrow-derived macrophages and in vivo in mice challenged intratracheally with LPS. Exposing LPS-stimulated RAW 264.7 mouse macrophages to FRT reduced TNF-α expression while increasing IL-1β expression despite the two genes sharing a common myeloid differentiation protein-88 (MyD88)-dependent pathway. Global activation of the three LPS-induced signaling intermediates that lead to cytokine gene expression, ERK and p38 MAPKs and NF-κB, was not affected by exposing RAW 264.7 cells to FRT as assessed by ERK and p38 phosphorylation and NF-κB in vitro DNA-binding activity and activation of a NF-κB-dependent synthetic promoter. However, chromatin immunoprecipitation (ChIP) analysis demonstrated that exposure to FRT reduced LPS-induced recruitment of NF-κB p65 to the TNF-α promoter while simultaneously increasing its recruitment to the IL-1β promoter. These data suggest that FRT exerts its effects on cytokine gene expression in a gene-specific manner through distal effects on promoter activation rather than proximal receptor activation and signal transduction.

scholarly journals Caspase-8 promotes c-Rel–dependent inflammatory cytokine expression and resistance againstToxoplasma gondii

2019 ◽  
pp. 201820529 ◽  
Author(s):  
Alexandra A. DeLaney ◽  
Corbett T. Berry ◽  
David A. Christian ◽  
Andrew Hart ◽  
Elisabet Bjanes ◽  
...  
Keyword(s):  
Gene Expression ◽  
Enzymatic Activity ◽  
Inflammatory Cytokine ◽  
Cytokine Expression ◽  
Cytokine Gene Expression ◽  
Caspase 8 ◽  
Cytokine Gene ◽  
Inflammatory Gene Expression ◽  
Inflammatory Gene ◽  
Monocyte Recruitment

Caspase-8 is a key integrator of cell survival and cell death decisions during infection and inflammation. Following engagement of tumor necrosis factor superfamily receptors or certain Toll-like receptors (TLRs), caspase-8 initiates cell-extrinsic apoptosis while inhibiting RIPK3-dependent programmed necrosis. In addition, caspase-8 has an important, albeit less well understood, role in cell-intrinsic inflammatory gene expression. Macrophages lacking caspase-8 or the adaptor FADD have defective inflammatory cytokine expression and inflammasome priming in response to bacterial infection or TLR stimulation. How caspase-8 regulates cytokine gene expression, and whether caspase-8–mediated gene regulation has a physiological role during infection, remain poorly defined. Here we demonstrate that both caspase-8 enzymatic activity and scaffolding functions contribute to inflammatory cytokine gene expression. Caspase-8 enzymatic activity was necessary for maximal expression ofIl1bandIl12b, but caspase-8 deficient cells exhibited a further decrease in expression of these genes. Furthermore, the ability of TLR stimuli to induce optimal IκB kinase phosphorylation and nuclear translocation of the nuclear factor kappa light chain enhancer of activated B cells family member c-Rel required caspase activity. Interestingly, overexpression of c-Rel was sufficient to restore expression of IL-12 and IL-1β in caspase-8–deficient cells. Moreover,Ripk3−/−Casp8−/−mice were unable to control infection by the intracellular parasiteToxoplasma gondii, which corresponded to defects in monocyte recruitment to the peritoneal cavity, and exogenous IL-12 restored monocyte recruitment and protection of caspase-8–deficient mice during acute toxoplasmosis. These findings provide insight into how caspase-8 controls inflammatory gene expression and identify a critical role for caspase-8 in host defense against eukaryotic pathogens.

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