scholarly journals Systemic LPS induces spinal inflammatory gene expression and impairs phrenic long-term facilitation following acute intermittent hypoxia

2013 ◽  
Vol 114 (7) ◽  
pp. 879-887 ◽  
Author(s):  
A. G. Huxtable ◽  
S. M. C. Smith ◽  
S. Vinit ◽  
J. J. Watters ◽  
G. S. Mitchell
Keyword(s):  
Gene Expression ◽  
Systemic Inflammation ◽  
Intermittent Hypoxia ◽  
Neural Control ◽  
Low Grade ◽  
Inflammatory Gene Expression ◽  
Inflammatory Gene ◽  
Long Term Facilitation ◽  
The Impact

Although systemic inflammation occurs in most pathological conditions that challenge the neural control of breathing, little is known concerning the impact of inflammation on respiratory motor plasticity. Here, we tested the hypothesis that low-grade systemic inflammation induced by lipopolysaccharide (LPS, 100 μg/kg ip; 3 and 24 h postinjection) elicits spinal inflammatory gene expression and attenuates a form of spinal, respiratory motor plasticity: phrenic long-term facilitation (pLTF) induced by acute intermittent hypoxia (AIH; 3, 5 min hypoxic episodes, 5 min intervals). pLTF was abolished 3 h (vehicle control: 67.1 ± 27.9% baseline; LPS: 3.7 ± 4.2%) and 24 h post-LPS injection (vehicle: 58.3 ± 17.1% baseline; LPS: 3.5 ± 4.3%). Pretreatment with the nonsteroidal anti-inflammatory drug ketoprofen (12.5 mg/kg ip) restored pLTF 24 h post-LPS (55.1 ± 12.3%). LPS increased inflammatory gene expression in the spleen and cervical spinal cord (homogenates and isolated microglia) 3 h postinjection; however, all molecules assessed had returned to baseline by 24 h postinjection. At 3 h post-LPS, cervical spinal iNOS and COX-2 mRNA were differentially increased in microglia and homogenates, suggesting differential contributions from spinal cells. Thus LPS-induced systemic inflammation impairs AIH-induced pLTF, even after measured inflammatory genes returned to normal. Since ketoprofen restores pLTF even without detectable inflammatory gene expression, “downstream” inflammatory molecules most likely impair pLTF. These findings have important implications for many disease states where acute systemic inflammation may undermine the capacity for compensatory respiratory plasticity.

scholarly journals Episode Frequency Determines the Impact of Chronic Intermittent Hypoxia on Phrenic Long Term Facilitation

2017 ◽  
Vol 31 (S1) ◽  
Author(s):  
Elisa Janine Gonzalez‐Rothi ◽  
Raphael Rodrigues Perim ◽  
Arash Tadjalli ◽  
Alec K Simon ◽  
Marissa Ciesla ◽  
...  
Keyword(s):  
Intermittent Hypoxia ◽  
Chronic Intermittent Hypoxia ◽  
Episode Frequency ◽  
Long Term Facilitation ◽  
The Impact

Abstract 458: Omega-3 Supplementation Does Not Affect Inflammatory Gene Expression in the Small Intestine of Patients with Type 2 Diabetes

2012 ◽  
Vol 32 (suppl_1) ◽  
Author(s):  
Marie-ève Labonté ◽  
Patrick Couture ◽  
André J Tremblay ◽  
Jean-Charles Hogue ◽  
Valéry Lemelin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Type 2 Diabetes ◽  
Small Intestine ◽  
Mrna Expression ◽  
Omega 3 ◽  
Inflammatory Gene Expression ◽  
Inflammatory Gene ◽  
Anti Inflammatory ◽  
The Impact

Recent evidence suggests that diet-induced inflammation in the small intestine is linked to obesity and insulin resistance. Long-chain omega-3 polyunsaturated fatty acids (LCn-3PUFA) such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been shown to have anti-inflammatory effects by down-regulating inflammatory gene expression in adipocytes and mononuclear cells. However, the extent to which EPA and DHA may exert their anti-inflammatory effects by down-regulating inflammation in the gut is unknown. The objective of the study was to investigate the impact of EPA+DHA supplementation on the expression of inflammatory genes in the small intestine of patients with type 2 diabetes. A total of 12 men with type 2 diabetes were recruited in this placebo-controlled randomized crossover study. After a 4-week run-in period, patients received in random sequence 5 g/d of fish oil providing 3 g of EPA+DHA or placebo (corn and soybean oil) for 8 weeks, each separated by a 12-week washout period. Gene expression was assessed by real-time PCR in duodenal biopsy samples obtained in the fasted state at the end of each treatment phase. Intestinal mRNA expression levels for interleukin(IL)-6 and tumor-necrosis factor(TNF)-α were hardly detectable after either treatment (< 100 copies/10^5 copies of the reference gene ATP synthase O subunit, ATP5o). Intestinal mRNA expression of IL-18 and of the transcription factor STAT3 (signal transducer and activator of transcription 3) was higher (> 5000 copies/10^5 copies ATP5o) but still relatively low and EPA+DHA supplementation had no impact on any of these levels (P ≥ 0.73 between treatments). Plasma C-reactive protein (CRP) concentrations after supplementation with EPA+DHA (5.2 ± 4.5 mg/L) were not significantly different than values measured after placebo (8.0 ± 10.8 mg/L, P = 0.2). In conclusion, these data suggest that gene expression of pro-inflammatory cytokines and STAT3 in duodenal cells is low in patients with type 2 diabetes and not affected by EPA+DHA supplementation.

Mice derived from in vitro αMEM-cultured preimplantation embryos exhibit postprandial hyperglycemia and higher inflammatory gene expression in peripheral leukocytes

2021 ◽  
Vol 85 (5) ◽  
pp. 1215-1226
Author(s):  
Shiori Ishiyama ◽  
Mayu Kimura ◽  
Nodoka Umihira ◽  
Sachi Matsumoto ◽  
Atsushi Takahashi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Postprandial Hyperglycemia ◽  
Postprandial Blood Glucose ◽  
Mrna Levels ◽  
Inflammatory Gene Expression ◽  
Inflammatory Gene ◽  
Peripheral Leukocytes ◽  
The Impact ◽  
Rice Diet

ABSTRACT We examined whether peripheral leukocytes of mice derived from in vitro αMEM-cultured embryos and exhibiting type 2 diabetes had higher expression of inflammatory-related genes associated with the development of atherosclerosis. Also, we examined the impact of a barley diet on inflammatory gene expression. Adult mice were produced by embryo transfer, after culturing two-cell embryos for 48 h in either α minimal essential media (α-MEM) or potassium simplex optimized medium control media. Mice were fed either a barley or rice diet for 10 weeks. Postprandial blood glucose and mRNA levels of several inflammatory genes, including Tnfa and Nox2, in blood leukocytes were significantly higher in MEM mice fed a rice diet compared with control mice. Barley intake reduced expression of S100a8 and Nox2. In summary, MEM mice exhibited postprandial hyperglycemia and peripheral leukocytes with higher expression of genes related to the development of atherosclerosis, and barley intake reduced some gene expression.

scholarly journals The impact of arousal state, sex, and sleep apnea on the magnitude of progressive augmentation and ventilatory long-term facilitation

2013 ◽  
Vol 114 (1) ◽  
pp. 52-65 ◽  
Author(s):  
Ziauddin Syed ◽  
Ho-Sheng Lin ◽  
Jason H. Mateika
Keyword(s):  
Sleep Apnea ◽  
Intermittent Hypoxia ◽  
Recovery Period ◽  
Apnea Hypopnea Index ◽  
Arousal State ◽  
Obstructive Sleep ◽  
End Tidal ◽  
Long Term Facilitation ◽  
The Impact

We examined the impact of arousal state, sex, and obstructive sleep apnea (OSA) on the magnitude of progressive augmentation of the hypoxic ventilatory response and ventilatory long-term facilitation (vLTF). We also examined whether exposure to intermittent hypoxia during sleep has an impact on the apnea-hypopnea index (AHI) in individuals with OSA. Ten men and seven women with OSA, along with ten healthy men and ten healthy women, were exposed to twelve 2-min episodes of hypoxia (end-tidal Po2: 50 Torr) in the presence of sustained hypercapnia (end-tidal Pco2: 3 Torr above baseline), followed by a 30-min recovery period during wakefulness and sleep. The OSA participants completed an additional sham study during sleep. The AHI during the first hour of sleep following the intermittent hypoxia and sham protocols were compared. Progressive augmentation was only evident during wakefulness and was enhanced in the OSA participants. vLTF was evident during wakefulness and sleep. When standardized to baseline, vLTF was greater during wakefulness and was enhanced in the OSA group (men: wakefulness 1.39 ± 0.08 vs. sleep 1.14 ± 0.03; women: wakefulness 1.35 ± 0.03 vs. sleep 1.16 ± 0.05 fraction of baseline; P ≤ 0.001) compared with control (men: wakefulness 1.19 ± 0.03 vs. sleep 1.09 ± 0.03; women: wakefulness 1.26 ± 0.05 vs. sleep 1.08 ± 0.04 fraction of baseline; P ≤ 0.001). The AHI following exposure to intermittent hypoxia was increased (intermittent hypoxia 72.8 ± 7.3 vs. sham 56.5 ± 7.0 events/h; P ≤ 0.01). Sex-related differences were not observed for the primary measures. We conclude that progressive augmentation is not evident, and the magnitude of vLTF is diminished during sleep compared with wakefulness in men and women. However, when present, the phenomena are enhanced in individuals with OSA. The AHI data indicate that, under the prevailing experimental conditions, vLTF did not serve to mitigate apnea severity.

scholarly journals P050 Effect of biological treatments (anti-TNFs) in the creeping fat of Crohn’s disease patients

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S158-S159
Author(s):  
D Montfort-Ferré ◽  
C Serena ◽  
M Millan ◽  
A Boronat-Toscano ◽  
E Maymó-Masip ◽  
...  
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Low Grade ◽  
Inflammatory Gene Expression ◽  
Histological Studies ◽  
Inflammatory Gene ◽  
Inflammatory Status ◽  
Mesenteric Fat

Abstract Background Crohn’s disease (CD) is characterized by persistent inflammation and ulcerations at the small or large bowel, provoking chronic low-grade systemic inflammation. Adipose tissue (AT) is believed to play an active role in the pathogenesis of CD, as the expansion of mesenteric fat attached to the inflamed segments of the intestine, also known as “creeping fat,” is a hallmark of the disease that seems to be directly related to disease activity. We demonstrated that adipose-stem cells (ASC) isolated from the creeping fat of CD patients showed a proinflammatory phenotype and increased the proliferation, migration, and phagocytic capacities of these cells. Taking into account the widely described effects of TNFalpha on the biology and functionality of adipocytes, we believe that biological therapies based on anti-TNF agents modify the inflammatory status of creeping fat. In this context, the effect of anti-TNF treatment on mesenteric fat is poorly studied, and the results are divergent. Methods Creeping fat biopsies were obtained from active CD patients that underwent surgery for symptomatic complications: 10 patients were on anti-TNF therapy (at least 6-months prior to surgery) and 10 patients never received any biological therapy. The groups were comparable in age, sex, and body mass index. We isolated from AT biopsies: AT explants, ASC, and adipose tissue macrophages (ATM). Adipose tissue was fixed in 10% phosphate-buffered formalin and embedded in paraffin for histological studies. The proliferation of ASC was performed using the CellTraceTM Violet Cell proliferation kit using flow cytometry and the cell migration of ASC was analyzed using a Tranwell system (8 mmpore polycarbonate membrane). Results Histological studies revealed that AT of patients treated with anti-TNF therapy recovered adipocytes morphology and showed lower infiltration of immune cells. Interestingly, we found a significant decrease in the gene expression of pro-inflammatory cytokines (IL1B, IL6, TNFA) in the creeping fat of CD patients treated with anti-TNF (Figure 1A). Furthermore, ATMs isolated from patients treated with anti-TNF showed a significant decrease in the gene expression of antigen-presenting markers (CD74, CIITa, HLA-DPB and HLA-DM) (Figure 1B). To note, ASC isolated from patients with anti-TNF therapy has significantly decreased their proliferation and migration capacities as well as the pro-inflammatory gene expression. Moreover, the anti-inflammatory gene expression and secretion were significantly increased in these cells (Figure 1C). Conclusion Anti-TNF therapies impact on the creeping fat of CD patients improving the phenotype of this tissue and this may cause a beneficial effect on CD.

scholarly journals Intrinsic Properties of Brown and White Adipocytes Have Differential Effects on Macrophage Inflammatory Responses

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Louisa Dowal ◽  
Pooja Parameswaran ◽  
Sarah Phat ◽  
Syamala Akella ◽  
Ishita Deb Majumdar ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcriptional Regulation ◽  
Inflammatory Responses ◽  
Low Grade ◽  
Brown Adipocytes ◽  
Inflammatory Gene Expression ◽  
Inflammatory Gene ◽  
Inflammatory Status ◽  
White Adipocytes ◽  
Inflammatory Profile

Obesity is marked by chronic, low-grade inflammation. Here, we examined whether intrinsic differences between white and brown adipocytes influence the inflammatory status of macrophages. White and brown adipocytes were characterized by transcriptional regulation of UCP-1, PGC1α, PGC1β, and CIDEA and their level of IL-6 secretion. The inflammatory profile of PMA-differentiated U937 and THP-1 macrophages, in resting state and after stimulation with LPS/IFN-gamma and IL-4, was assessed by measuring IL-6 secretion and transcriptional regulation of a panel of inflammatory genes after mono- or indirect coculture with white and brown adipocytes. White adipocyte monocultures show increased IL-6 secretion compared to brown adipocytes. White adipocytes cocultured with U937 and THP-1 macrophages induced a greater increase in IL-6 secretion compared to brown adipocytes cocultured with both macrophages. White adipocytes cocultured with macrophages increased inflammatory gene expression in both types. In contrast, macrophages cocultured with brown adipocytes induced downregulation or no alterations in inflammatory gene expression. The effects of adipocytes on macrophages appear to be independent of stimulation state. Brown adipocytes exhibit an intrinsic ability to dampen inflammatory profile of macrophages, while white adipocytes enhance it. These data suggest that brown adipocytes may be less prone to adipose tissue inflammation that is associated with obesity.

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