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.

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 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 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 Inflammatory Response in COVID-19 Patients Resulting from the Interaction of the Inflammasome and SARS-CoV-2

2021 ◽  
Vol 22 (15) ◽  
pp. 7914
Author(s):  
So Yeong Cheon ◽  
Bon-Nyeo Koo
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Inflammatory Response ◽  
Immune Complex ◽  
Inflammatory Cytokines ◽  
Immune Cells ◽  
Organ Damage ◽  
Cytokine Storm ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
Pro Inflammatory Cytokines

The outbreak of the coronavirus disease 2019 (COVID-19) began at the end of 2019. COVID-19 is caused by infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and patients with COVID-19 may exhibit poor clinical outcomes. Some patients with severe COVID-19 experience cytokine release syndrome (CRS) or a cytokine storm—elevated levels of hyperactivated immune cells—and circulating pro-inflammatory cytokines, including interleukin (IL)-1β and IL-18. This severe inflammatory response can lead to organ damage/failure and even death. The inflammasome is an intracellular immune complex that is responsible for the secretion of IL-1β and IL-18 in various human diseases. Recently, there has been a growing number of studies revealing a link between the inflammasome and COVID-19. Therefore, this article summarizes the current literature regarding the inflammasome complex and COVID-19.

scholarly journals Identification of Atypical Mitogen-Activated Protein Kinase MAPK4 as A Novel Regulator in Acute Lung Injury

2020 ◽  
Author(s):  
Ling Mao ◽  
Ya Zhou ◽  
Longqing Chen ◽  
Lin Hu ◽  
Shiming Liu ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Survival Time ◽  
Inflammatory Cytokines ◽  
Mitogen Activated Protein Kinase ◽  
Lps Challenge ◽  
Mitogen Activated Protein ◽  
Pre Treatment ◽  
Pro Inflammatory Cytokines

Abstract Background: Acute lung injury (ALI) is a serious disease with highly morbidity and mortality that causes serious health problems worldwide. Atypical mitogen activated protein kinases (MAPKs) play critical roles in the development of tissues and have been proposed as promising therapeutic targets for various diseases. However, the potential role of atypical MAPKs in ALI remains elusive. In this study, we investigated the role of atypical MAPKs family member MAPK4 in ALI using LPS-induced murine ALI model. Results: We found that MAPK4 deficiency mice exhibited prolonged survival time after LPS challenge, accompanied by alleviated pathology in lung tissues, decreased levels of pro-inflammatory cytokines and altered composition of immune cells in BALF. Furthermore, the transduction of related signaling pathways, including MK5, AKT, JNK, and p38 MAPK pathways, was reduced obviously in LPS-treated MAPK4-/- mice. Notably, the expression of MAPK4 was up-regulated in lung tissues of ALI model, which was not related with MAPK4 promoter methylation, but negatively orchestrated by transcriptional factors NFKB1 and NR3C1. Further studies have shown that the expression of MAPK4 was also increased in LPS-treated macrophages. Meanwhile, MAPK4 deficiency reduced the expression of related pro-inflammatory cytokines in macrophage in response to LPS treatment. Finally, MAPK4 inhibition using shRNA pre-treatment could ameliorate the pathology of lung tissues and prolong the survival time of mice after LPS challenge. Conclusions: Collectively, these findings reveal an important biological function of atypical MAPK in mediating the pathology of ALI, indicating that MAPK4 might be a novel potential therapeutic target for ALI treatment.

scholarly journals Significance of the determination of proinflammatory cytokines in the serum of polytraumatized patients with sepsis

2004 ◽  
Vol 61 (2) ◽  
pp. 137-143 ◽  
Author(s):  
Maja Surbatovic ◽  
Krsta Jovanovic ◽  
Danilo Vojvodic ◽  
Nikola Filipovic ◽  
Dragan Babic
Keyword(s):  
Inflammatory Response ◽  
Inflammatory Cytokines ◽  
Clinical Investigation ◽  
Intensive Therapy ◽  
Multiple Organ ◽  
Mean Values ◽  
Reliable Predictor ◽  
Necrosis Factor ◽  
Pro Inflammatory Cytokines

Severe sepsis and trauma complicated with multiple organ dysfunction syndrome (MODS) are among the leading causes of death in intensive therapy units with mortality rate exceeding 50%. The outcome is not determined only by infection or trauma, but also by the intensity of immuno-inflammatory response, which is essential for host defence, but if uncontrolled leads to MODS. Pro-inflammatory cytokines (tumor necrosis factor-a -TNF-a, IL-1 IL-8, IL-12, IFN-g, etc) represent a part of this immuno-inflammatory response to an insult. The results of the clinical investigation of correlation between pro-inflammatory cytokines (IL-8, IL-12, TNF-a, IFN-g) the outcome (survivors, non-survivors), and the severity (systemic inflammatory response syndrome - SIRS - less severe, and MODS - more severe) in polytraumatised patients with sepsis are presented in this paper. Mean values of IL-8 were 1.3-fold higher in non-survivors (p<0.05), and 60-fold higher in MODS group (p<0.01). Mean values of IL-12 were 1.6-fold higher in survivors (p<0.01), while the values between SIRS and MODS group did not differ significantly; mean values of TNF-a were 3-fold higher in survivors (p<0.05), and 46-fold higher in MODS group (p<0.01). Mean values of IFN-g did not differ significantly between the two groups regarding the outcome and severity. The obtained results indicated that IL-8 was a reliable predictor of lethal outcome and MODS (p<0.01), IL-12 a reliable predictor of survival (p<0.05), and TNF-a a reliable predictor of survival (p<0.05) and MODS (p<0.01).

scholarly journals Implication of HisF fromAcinetobacter baumanniiin persistence during a pneumonia infection

2019 ◽  
Author(s):  
Marta Martínez-Guitián ◽  
Juan C. Vázquez-Ucha ◽  
Laura Álvarez-Fraga ◽  
Kelly Conde-Pérez ◽  
Juan A. Vallejo ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Mutant Strain ◽  
Inflammatory Cytokines ◽  
Negative Regulator ◽  
Host Inflammatory Response ◽  
Pro Inflammatory Cytokines

ABSTRACTThehisFgene fromA. baumanniiATCC 17978 was found over-expressed during a murine pneumonia infection. A mutant strain lackinghisFshowed its involvement in virulence during mice pneumonia as well as in host inflammatory response, where the product of HisF may act as negative regulator in the production of pro-inflammatory cytokines. This work evaluates the role of HisF in theA. baumanniipathogenesis and suggests its potential as a new target for antimicrobial therapies.

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