scholarly journals IRF5 is increased in labouring myometrium and regulates pro-labour mediators

Reproduction ◽  
2018 ◽  
Vol 156 (3) ◽  
pp. 207-218
Author(s):  
Ratana Lim ◽  
Gillian Barker ◽  
Martha Lappas
Keyword(s):  
Preterm Birth ◽  
Inflammatory Response ◽  
Inflammatory Cytokines ◽  
Treatment Options ◽  
Adult Life ◽  
Human Myometrium ◽  
Myometrial Cells ◽  
Associated Proteins ◽  
Term Labour ◽  
Pro Inflammatory Cytokines

Preterm birth continues to be the leading cause of neonatal mortality and morbidities that can extend into adult life. Few treatment options stem from our incomplete understanding of the mechanisms of human labour and delivery. Activation of the inflammatory response in gestational tissues by inflammation and/or infection leads to the production of pro-inflammatory and pro-labour mediators, thus preterm birth. Interferon regulatory factor 5 (IRF5) has recently emerged as an important pro-inflammatory transcription factor involved in acute and chronic inflammation. The aims of this study were to determine the expression of IRF5 in human myometrium from labouring and non-labouring women, and whether IRF5 is involved in the genesis of pro-inflammatory and pro-labour mediators induced by pro-inflammatory cytokines or toll-like receptor (TLR) ligands. IRF5 mRNA and protein expression was significantly higher in human myometrium after spontaneous term labour, compared to non-labouring tissues. IRF5 mRNA expression was also significantly higher in primary myometrial cells treated with the pro-inflammatory cytokines IL1B or TNF. In primary myometrial cells, IRF5 knockdown by siRNA (siIRF5) was associated with significantly decreased expression and or secretion of pro-inflammatory cytokines (IL1A, IL6), chemokines (CXCL8, CCL2), adhesion molecules (ICAM1, VCAM1) and contraction-associated proteins PTGS2, PGF2α and PTGFR when in the presence of IL1B, TNF, fsl-1 (TLR2/6 ligand) or flagellin (TLR5 ligand). siIRF5-transfected cells also displayed decreased NF-κB RELA transcriptional activity in the presence of these preterm birth mediators. Our study suggests a novel role for IRF5 in the regulation of the inflammatory response in human myometrium.

scholarly journals Focal intra-colon cooling reduces organ injury and systemic inflammation after REBOA management of lethal hemorrhage in rats

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Awadhesh K. Arya ◽  
Kurt Hu ◽  
Lalita Subedi ◽  
Tieluo Li ◽  
Bingren Hu
Keyword(s):  
Inflammatory Response ◽  
Inflammatory Cytokines ◽  
Troponin I ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Balloon Catheter ◽  
Organ Injury ◽  
Upper Body ◽  
Anti Inflammatory ◽  
Pro Inflammatory Cytokines

AbstractResuscitative endovascular balloon occlusion of the aorta (REBOA) is a lifesaving maneuver for the management of lethal torso hemorrhage. However, its prolonged use leads to distal organ ischemia–reperfusion injury (IRI) and systemic inflammatory response syndrome (SIRS). The objective of this study is to investigate the blood-based biomarkers of IRI and SIRS and the efficacy of direct intestinal cooling in the prevention of IRI and SIRS. A rat lethal hemorrhage model was produced by bleeding 50% of the total blood volume. A balloon catheter was inserted into the aorta for the implementation of REBOA. A novel TransRectal Intra-Colon (TRIC) device was placed in the descending colon and activated from 10 min after the bleeding to maintain the intra-colon temperature at 37 °C (TRIC37°C group) or 12 °C (TRIC12°C group) for 270 min. The upper body temperature was maintained at as close to 37 °C as possible in both groups. Blood samples were collected before hemorrhage and after REBOA. The organ injury biomarkers and inflammatory cytokines were evaluated by ELISA method. Blood based organ injury biomarkers (endotoxin, creatinine, AST, FABP1/L-FABP, cardiac troponin I, and FABP2/I-FABP) were all drastically increased in TRIC37°C group after REBOA. TRIC12°C significantly downregulated these increased organ injury biomarkers. Plasma levels of pro-inflammatory cytokines TNF-α, IL-1b, and IL-17F were also drastically increased in TRIC37°C group after REBOA. TRIC12°C significantly downregulated the pro-inflammatory cytokines. In contrast, TRIC12°C significantly upregulated the levels of anti-inflammatory cytokines IL-4 and IL-10 after REBOA. Amazingly, the mortality rate was 100% in TRIC37°C group whereas 0% in TRIC12°C group after REBOA. Directly cooling the intestine offered exceptional protection of the abdominal organs from IRI and SIRS, switched from a harmful pro-inflammatory to a reparative anti-inflammatory response, and mitigated mortality in the rat model of REBOA management of lethal hemorrhage.

The Protective Effect of Picroside II on Isoflurane-Induced Neuronal Injury in Rats via Downregulating miR-195

2021 ◽  
pp. 1-9
Author(s):  
Hui Li ◽  
Weijia Du ◽  
Yawei Yuan ◽  
Jingjing Xue ◽  
Qiang Li ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Protective Effect ◽  
Inflammatory Cytokines ◽  
Escape Latency ◽  
Neuronal Cells ◽  
Neuronal Injury ◽  
Morris Water Maze Test ◽  
Picroside Ii ◽  
Tnf Α ◽  
Pro Inflammatory Cytokines

<b><i>Introduction:</i></b> Numerous pieces of evidence demonstrated that isoflurane induces hippocampal cell injury and cognitive impairments. Picroside II has been investigated for its anti-apoptosis and antioxidant neuroprotective effects. We aimed to explore the protective effects of picroside II and the role of microRNA-195 (miR-195) on isoflurane-induced neuronal injury in rats. <b><i>Methods:</i></b> The Morris water maze test was used to evaluate the effects of isoflurane on rats regarding escape latency and time in quadrant parameters. Real-time quantitative PCR was used to detect the expression levels of miR-195 and pro-inflammatory cytokines, including inter­leukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) mRNA, in the hippocampal tissues and neuronal cells. <b><i>Results:</i></b> The picroside II significantly improves isoflurane-induced higher escape latency and lower time spent in the quadrant compared with the control rats. Picroside II also promotes cell viability and suppresses cell apoptosis of isoflurane-induced neuronal cells. Besides, picroside II suppresses the expression of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) and miR-195 in vivo and in vitro. Furthermore, overexpression of miR-195 abrogates the effects of picroside II on the expression of pro-inflammatory cytokines. The appropriate dose of picroside II is 20 mg/kg. <b><i>Conclusion:</i></b> Picroside II could protect the nervous system possibly through inhibiting the inflammatory response in the isoflurane-induced neuronal injury of rats. The protective effect of picroside II may be achieved by downregulating the expression of miR-195 and then inhibiting the inflammatory response.

scholarly journals A pronounced uterine pro-inflammatory response at parturition is an ancient feature in mammals

2017 ◽  
Vol 284 (1865) ◽  
pp. 20171694 ◽  
Author(s):  
Victoria L. Hansen ◽  
Lauren S. Faber ◽  
Ali A. Salehpoor ◽  
Robert D. Miller
Keyword(s):  
Immune System ◽  
Inflammatory Response ◽  
Inflammatory Cytokines ◽  
Immune Regulation ◽  
Monodelphis Domestica ◽  
Immune Gene ◽  
Invasive Placenta ◽  
Gene Transcripts ◽  
Pro Inflammatory Cytokines

Regulating maternal immunity is necessary for successful human pregnancy. Whether this is needed in mammals with less invasive placentation is subject to debate. Indeed, the short gestation times in marsupials have been hypothesized to be due to a lack of immune regulation during pregnancy. Alternatively, the maternal marsupial immune system may be unstimulated in the absence of a highly invasive placenta. Transcripts encoding pro-inflammatory cytokines were found to be overrepresented in the whole uterine transcriptome at terminal pregnancy in the opossum, Monodelphis domestica . To investigate this further, immune gene transcripts were quantified throughout opossum gestation. Transcripts encoding pro-inflammatory cytokines remained relatively low during pre- and peri-attachment pregnancy stages. Levels dramatically increased late in gestation, peaking within 12 h prior to parturition. These results mirror the spike of inflammation seen at eutherian parturition but not at attachment or implantation. Our results are consistent with the role of pro-inflammatory cytokines at parturition being an ancient and conserved birth mechanism in therian mammals.

scholarly journals The effect of early resuscitation and ulinastatin on the severe acute pancreatitis in obese patients

2020 ◽  
Vol 24 (3) ◽  
pp. 449-454
Author(s):  
O. Tkachuk ◽  
A. Kebkalo
Keyword(s):  
Acute Pancreatitis ◽  
Inflammatory Response ◽  
Inflammatory Cytokines ◽  
Severe Acute Pancreatitis ◽  
Interleukin 1 ◽  
Obese Patients ◽  
Ringer’S Lactate ◽  
Bed Days ◽  
Experimental Group ◽  
Pro Inflammatory Cytokines

Annotation. Obesity is a problem of the third millennium. It is known that obesity is a major factor in the development of various diseases, including acute pancreatitis. Obesity itself is a pro-inflammatory condition with elevated levels of the following pro-inflammatory cytokines: tumor necrosis factor (TNF-a), interleukin (IL) IL-10, IL-6, IL-1b. Acute pancreatitis is also a disease based on the pathogenesis of the cytokine reaction and autolysis. Thus, against the background of the already formed inflammatory response, the inflammatory response intensifies and increases, and the level of pro-inflammatory cytokines reaches critical values. The purpose is to study the effect of ulinastatin on the severe acute pancreatitis in obese patients. To refute or confirm the hypothesis among patients with severe acute pancreatitis and obesity (BMI was 37.48±2.19 kg / m2), two groups were randomized. In the first group (experimental) of 18 patients, a step-up approach was performed. In the second group (control), the total number of which was 18 patients, a standard treatment algorithm was performed. The experimental group suggested the use of early resuscitation with Ringer’s lactate and ulinastatin in the first 5 days of the disease. The drug was administered at a dose of 200,000 IU by intravenous infusion for 1 hour 3 times a day for 5 days. In the control group, resuscitation was performed with 0.9% sodium chloride solution without the use of ulinastatin. Hypothesis was tested by monitoring procalciton and C-reactive protein, interleukin-1 and interleukin-6 over a period of 24 hours, 48 hours, 10 days, 15 days, 30 days, 45 and 60 days. The choice of procalcitonin and CRP was made by calculating the relative risk, as the level of CRP> 200mg / l indicated the preservation of severe disease (RR=2.07; 95% CI=1.65-2.59; p=0.01), and an increase in procalcitonin> 1.8 ng / mg was a predictor of infection (RR=2.27; 95% CI=1.083-4.769; p=0.02). The use of ulinastatin during the first 5 days in the experimental group reduced the level of interleukin-1 from 23.64±4.13 to 8.71±2.49 pg / ml (p=0.001; α=0.05), interleukin- 6 – from 29.72±4.27 to 12.43±2.36 pg / ml (p=0.001; α=0.05). The use of resuscitation with Ringer's lactate solution in combination with ulinastatin for 5 days helped to reduce the level of procalciton in 1.8 times (2.89±0.88 compared with 1.8±0.23 ng / mg; p=0.001; α=0.05). The level of CRP during the period of ulinastatin decreased by 41.68 (267.28±114.11 compared with 225.6±84.9 mg / l; p=0.01; α=0.05). In-hospital mortality was significantly lower in the ulinastatin group (16% vs. 69.6%; p=0.0003; α=0.05). Significantly lower proportion of patients (24% compared to 73.9%; p=0.0005; α=0.05) with multiple organ failure among the study group. Organ dysfunction was acquired on day 5 among patients taking ulinastatin. The length of hospital stay was 49.7±4.2 bed-days, while in the comparison group – 56.67±5.84 bed-days (p=0.01; α=0.05). Thus, the use of Ringer-lactate early resuscitation in combination with ulinastatin has improved the treatment of severe acute pancreatitis in obese patients.

scholarly journals The short-chain fatty acids butyrate and propionate protect against inflammation-induced activation of mediators involved in active labor: implications for preterm birth

2020 ◽  
Vol 26 (6) ◽  
pp. 452-468 ◽  
Author(s):  
Hope Eveline Carter Moylan ◽  
Caitlyn Nguyen-Ngo ◽  
Ratana Lim ◽  
Martha Lappas
Keyword(s):  
Fatty Acids ◽  
Preterm Birth ◽  
Inflammatory Cytokines ◽  
Short Chain Fatty Acids ◽  
Short Chain ◽  
Fetal Membranes ◽  
Spontaneous Preterm Birth ◽  
Anti Inflammatory ◽  
Pro Inflammatory Cytokines ◽  
Chain Fatty Acids

Abstract Spontaneous preterm birth is a global health issue affecting up to 20% of pregnancies and leaves a legacy of neurodevelopmental complications. Inflammation has been implicated in a significant proportion of preterm births, where pro-inflammatory insults trigger production of additional pro-inflammatory and pro-labor mediators. Thus, novel therapeutics that can target inflammation may be a novel avenue for preventing preterm birth and improving adverse fetal outcomes. Short-chain fatty acids (SCFAs), such as butyrate and propionate, are dietary metabolites produced by bacterial fermentation of fiber in the gut. SCFAs are known to possess anti-inflammatory properties and have been found to function through G-coupled-receptors and histone deacetylases. Therefore, this study aimed to investigate the effect of SCFAs on pro-inflammatory and pro-labor mediators in an in vitro model of preterm birth. Primary human cells isolated from myometrium and fetal membranes (decidua, amnion mesenchymal and amnion epithelial cells) were stimulated with the pro-inflammatory cytokines tumor necrosis factor alpha (TNF) or interleukin 1B (IL1B). The SCFAs butyrate and propionate suppressed inflammation-induced expression of pro-inflammatory cytokines and chemokines, adhesion molecules, the uterotonic prostaglandin PGF2alpha and enzymes involved in remodeling of myometrium and degradation of the fetal membranes. Notably, propionate and butyrate also suppressed inflammation-induced prostaglandin signaling and myometrial cell contraction. These effects appear to be mediated through suppression of nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) activation. These results suggest that the SCFAs may be able to prevent myometrial contractions and rupture of membranes. Further in vivo studies are warranted to identify the efficacy of SCFAs as a novel anti-inflammatory therapeutic to prevent inflammation-induced spontaneous preterm birth.

scholarly journals Vitamin D Elicits Anti-Inflammatory Response, Inhibits Contractile-Associated Proteins, and Modulates Toll-Like Receptors in Human Myometrial Cells

2012 ◽  
Vol 20 (4) ◽  
pp. 463-475 ◽  
Author(s):  
Chandrasekhar Thota ◽  
Takeisha Farmer ◽  
Robert E. Garfield ◽  
Ramkumar Menon ◽  
Ayman Al-Hendy
Keyword(s):  
Vitamin D ◽  
Inflammatory Response ◽  
Toll Like Receptors ◽  
Myometrial Cells ◽  
Associated Proteins ◽  
Anti Inflammatory

Regulation of neutrophil apoptosis by Mcl-1

2004 ◽  
Vol 32 (3) ◽  
pp. 489-492 ◽  
Author(s):  
S.W. Edwards ◽  
M. Derouet ◽  
M. Howse ◽  
R.J. Moots
Keyword(s):  
Inflammatory Response ◽  
Survival Time ◽  
Inflammatory Cytokines ◽  
Turnover Rate ◽  
Neutrophil Apoptosis ◽  
Spontaneous Apoptosis ◽  
High Turnover ◽  
Apoptotic Protein ◽  
Local Oxygen ◽  
Pro Inflammatory Cytokines

Neutrophils rapidly undergo spontaneous apoptosis, but this process can be considerably delayed by exposure to a variety of agents such as pro-inflammatory cytokines. The anti-apoptotic protein of the Bcl-2 family, Mcl-1, plays a key role in the regulation of neutrophil apoptosis. The protein has some unusual properties compared with other family members, including an extremely high turnover rate. Many factors, such as cytokines and local oxygen concentrations, can regulate cellular levels of Mcl-1 via transcription and post-transcriptional modification, control the survival time of neutrophils within tissues and thereby influence the inflammatory response.

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