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.

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 Heme Overload Triggers Xanthine Oxidase Release and Mediates the Inflammatory Response

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3529-3529
Author(s):  
Heidi M Schmidt ◽  
Eric Kelley ◽  
Adam Straub
Keyword(s):  
Inflammatory Response ◽  
Inflammatory Cytokines ◽  
Organ Damage ◽  
Heme Binding ◽  
Qrt Pcr ◽  
Hematological Analysis ◽  
Lung And Kidney ◽  
Pro Inflammatory Cytokines

Heme crisis drives a number of hemolytic conditions including malaria, sepsis, blood transfusions, and cardiac bypass. Free heme, released from hemoglobin, causes endothelial damage via direct and iron (Fe)-mediated generation of reactive species, as well as activation of endothelial cells and macrophages leading to an inflammatory response. An enzyme that has been shown to have elevated activity in many hemolytic conditions is xanthine oxidase (XO). XO generates hydrogen peroxide (H2O2) as a byproduct of the oxidation of hypoxanthine and xanthine in the final steps of the purine degradation pathway. While XO activity is known to be increased in hemolytic diseases, its exact role has yet to be established. In order to study the role of XO in hemolytic disease, we developed a novel model of heme crisis in which we injected mice with two identical doses of hemin one hour apart and monitored the mice for 24 hours in order to deplete heme scavenging mechanisms before inducing heme crisis. Heme crisis induced damage was evaluated by hemopexin ELISA, plasma XO activity by HPLC, H&E staining of liver, lung, and kidney tissue, qRT-PCR of inflammatory cytokines, and hematological analysis of circulating leukocytes, RBCs, and platelets. To isolate the role of XO, our heme crisis model was repeated; however, prior to hemin injection mice were pretreated with the FDA approved, XO inhibitor febuxostat (10 mg/kg/day) in drinking water. Liver, lung and kidney injury and inflammation was again evaluated with H&E staining, qRT-PCR of inflammatory cytokines, and hematological analysis. In addition, the interaction between heme and XO was explored in vitro using evaluation of hemin degradation via spectrophotometry and computational modeling. We found that mice treated with two doses of 50 μmol/kg hemin had a 92.3% decrease in hemopexin, and a 20-fold increase in plasma XO activity compared to controls. H&E staining showed severe liver hemorrhaging, increased cell infiltration in the lung, and cellular disorganization in the kidney. The pro-inflammatory cytokines, IL-6, TNFα, and IL-1β, were all significantly increased in the liver, lung, and kidney, with IL-6 having the greatest fold change in all three organs. Systemic inflammation was also suggested via significant increases in circulating monocytes and granulocytes. Additionally, hematological analysis showed decreased RBCs and platelets, indicating additional hemolysis and platelet activation. While these markers of injury and inflammation were observed with 50 μmol/kg hemin, lower doses of hemin showed no effect. Together, these results indicate that our heme crisis model mimics the pro-inflammatory state, and organ damage observed in patients during severe hemolysis. Interestingly, when mice were pre-treated with febuxostat, organ damage was observed at lower doses of hemin (25 μmol/kg) compared to untreated mice, as observed by H&E staining. Inhibition of XO also had a significant impact on the inflammatory response. While circulating monocytes were decreased in mice pre-treated with febuxostat, the pro-inflammatory cytokines IL-6, TNFα, and IL-1β, were further exacerbated in the liver, lung, and kidney. This suggests that XO may play a role in mediating the inflammatory response induced by heme crisis. To explore how XO could mediate the inflammatory response we conducted in vitro enzymatic XO experiments with hemin. We found that XO was able to degrade hemin as observed by a decrease in absorbance at 618 nm. Additionally, based on a spectral shift observed when hemin and XO were incubated together, we hypothesized that XO may have the ability to bind hemin. This was further supported by computational modeling in which a potential heme binding site was discovered in the FAD domain of XO with a kd=128 nM. This suggests that XO may have the ability to bind hemin. Thus, during substrate oxidation, H2O2 is produced in the same XO domain of the potential heme binding site, allowing for increased chance of the H2O2 induced heme splitting reaction. We further hypothesize that the uric acid produced by xanthine oxidation may serve as an Fe chelator to scavenge free Fe released by a heme splitting reaction. By creating a microenvironment that can split heme and scavenge Fe, XO may be able to mediate the inflammatory response induced by heme crisis. Disclosures Straub: Bayer Pharmaceuticals: Research Funding.

The role of inflammatory cytokines in the pathogenesis of premature labor in multiple pregnancy as a result of ART

2016 ◽  
pp. 73-76
Author(s):  
B.M. Ventskivskiy ◽  
◽  
I.V. Poladych ◽  
S.O. Avramenko ◽  
◽  
...  
Keyword(s):  
Assisted Reproductive Technology ◽  
Inflammatory Cytokines ◽  
Proinflammatory Cytokines ◽  
Local Level ◽  
Multiple Pregnancy ◽  
Reproductive Technology ◽  
System Level ◽  
Premature Labor ◽  
Pro Inflammatory Cytokines

In recent years there has been an increase in the frequency of multiple pregnancies and the associated perinatal losses. It is a result of multiple pregnancy in ART refers to a high-risk gestation, at which premature births occur in 2 times more often than in singleton pregnancies. The objective: to determine the role of pro-inflammatory cytokines in the pathogenesis of premature labor in multiple pregnancy, as a result of assisted reproductive technology. Patients and methods. to determine the pro-inflammatory cytokines that all pregnant with bagtopliddyam held immunosorbent assay, defined concentrations of interleukin (IL) in serum and cervical mucus. Results. The analysis of the levels of pro-inflammatory cytokines (IL-1, IL-8) in the test environment, found high concentrations in the surveyed women with multiple pregnancy, due to the use of ART, compared with spontaneous multiple and singleton pregnancy. Increased concentration of proinflammatory cytokines in patients with multiple pregnancy by ART is associated with their synthesis at the system level, it stimulated foci of inflammation in the female genitals and extragenital localization. This correlates with the clinical data and statistical analysis, patients with multiple pregnancy as a result of ART had weighed infectious-inflammatory history. Conclusion. The study showed that elevated levels of proinflammatory cytokines in the systemic and local level in patients with multiple pregnancy due to ART, typical for women with miscarriage, because of the physiological course of pregnancy characterized by the predominance of anti-inflammatory cytokines that prevent rejection of the fetus as a foreign factor. Based on the data obtained proved the role of systemic inflammatory factors in the genesis of preterm labor in women with a multiple pregnancy, as a result of assisted reproductive technology. Key words: multiple pregnancy, assisted reproductive technology, premature birth, interleukine-1, interleukine-8.

scholarly journals Evaluation of the role of CD47 in sickle cell disease

2021 ◽  
Author(s):  
Basmah Eldakhakhny ◽  
Hadeel Al Sadoun ◽  
Nehal Bin Taleb ◽  
Dunya Ahmed Nori ◽  
Nawal Helmi ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Annexin V ◽  
Cell Disease ◽  
Phagocytic Cells ◽  
Surface Marker Expression ◽  
Inflammatory Phenotype ◽  
Healthy Control ◽  
Cell Surface Marker Expression ◽  
Pro Inflammatory Cytokines

AbstractCD47 is a self-marker expressed on the surface of RBCs and work to prevent the process of phagocytosis. SIRPα is the ligand of CD47 that is expressed on the surface of phagocytic cells, such as macrophages, to control the removal of dead/diseased cells. This study aimed to examine the expression of CD47 on RBCs and SIRPα on PBMC cells in SCD patients and the apoptosis of SCD RBCs. We also measured the levels of pro-inflammatory cytokines in SCD patients and correlated it with the cell surface marker expression of CD47 and SIRPα to determine whether CD47 and/or SIRPα played a role in promoting the pro-inflammatory phenotype in SCD. Whole blood samples were drawn from SCD patients, and healthy control and PBMC were isolated and stained with SIRPα. Change in CD47, apoptosis by annexin V marker, and pro-inflammatory cytokines were measured and correlation among these variants was determined. The expression of CD47 was significantly decreased and the apoptosis was increased in RBCs of SCD patients. A higher level of pro-inflammatory cytokines, IL-6 and IL-1β, was found in SCD patients and IL-1β was found to be inversely correlated with SIRPα expression. Our data showed that CD47 of erythrocytes of SCD samples is reduced and that the apoptosis is increased in those patients. Based on the role of CD47, we suggest that increased apoptosis in SCD would be impacted by the reduced level of CD47. An inverse relationship was found between SIRPα marker on PBMC and the increased production of pro-inflammatory cytokines in SCD.

scholarly journals AB0827 SERUM NESPHATIN-1 IN PATHOGENESIS RHEUMATOID ARTHRITIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1437.2-1438
Author(s):  
T. Kvlividze ◽  
V. Polyakov ◽  
В. Zavodovsky ◽  
Y. Polyakova ◽  
L. Seewordova ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Blood Serum ◽  
Inflammatory Cytokines ◽  
Inflammatory Markers ◽  
Healthy People ◽  
Healthy Individuals ◽  
Markers Of Inflammation ◽  
High Level ◽  
Pro Inflammatory Cytokines

Background:Interest in highly specialized tissue cytokines contributed to the discovery of new biologically active molecules. Nesfatin-1 (NF) - discovered in 2006 as an anorexigenic factor. NF-1 is believed to be involved in the regulation of energy homeostasis by regulating appetite and water intake. The role of NF-1 in the pathogenesis of inflammatory diseases is poorly understood. Recently, studies have found a relationship between an increased level of NF-1 and inflammatory markers in various pathologies.Objectives:Study of the level of nesfatin-1 in the blood serum of healthy people, determination of the correlation between the level of NF-1 with the severity of clinical symptoms and classic markers of inflammation in patients with RA.Methods:120 persons were examined: 90 patients with RA and 30 healthy people. All patients underwent a complete clinical and laboratory examination. Plasma NF-1 levels were determined using commercial test systems (RaiBiotech, cat # EIA-NESF) according to the manufacturer’s instructions. Patients with various forms of RA were comparable in age to the group of healthy individuals. Statistical processing of clinical examination data was carried out using the “STATISTICA 10.0 for Windows” software package. Quantitative data were processed statistically using the parametric Student’s t-test, qualitative data using the non-parametric chi-square test. The significance of differences between groups was determined using analysis of variance. The results were considered statistically significant at p <0.05.Results:The average level of NF-1 in blood serum in healthy individuals was 31.79 ± 3.21 ng / ml (M ± σ). The level of normal NF-1 values in healthy individuals, defined as M ± 2σ, ranged from 25.3 to 37.83 ng / ml. There was no significant difference in the levels of circulating NF-1 and BMI in healthy individuals and patients with RA (p> 0.05). The inverse relationship of a lower level of NF-1 with an increase in BMI was not significant.Group 1 (66 patients with RA) with increased serum NF-1 levels (> 37.83 ng / ml), and group 2 (44 patients) with normal values (<37.83 ng / ml). A high level of NF-1 was characteristic for patients with high activity according to DAS28, RF seropositive, ACCP-positive, with extra-articular manifestations, who had been ill for 10 years or more. A reliable relationship between the level of NF-1 in the blood serum and laboratory parameters of RA activity - ESR, CRP, was shown, and secondary synovitis was more common. Our data show a direct correlation between the NF-1 level of the pro-inflammatory markers of RA.Conclusion:The positive correlation between the level of NF-1 and classical markers of inflammation, such as CRP and ESR, confirms the involvement of NF-1 in the pathophysiology of inflammation in RA. This is also evidenced by the correlation of a high level of NF-1 in the blood serum with a more severe clinical picture of RA. It is known that NF-1 can promote the release of pro-inflammatory cytokines such as interleukin-8 (IL-8), interleukin-6 (IL-6), and macrophage inflammatory protein-1a (MIP-1a) in the chondrocytes of RA patients.It is necessary to further study the role of NF-1 in the pathogenesis of systemic inflammatory reactions and the possibility of targeting pro-inflammatory cytokines, the possibility of regulating the level of NF-1 by drugs.References:[1]Kvlividze T.Z., Zavodovsky B.V., Akhverdyan Yu.R. Kvlividze T.Z., Zavodovsky B.V., Akhverdyan Yu.R., Polyakova Yu.V., Sivordova L.E., Yakovlev A.T., Zborovskaya I.A. Serum nesfatin -1 as a marker of systemic inflammation in rheumatoid arthritis. Klinicheskaya Laboratornaya Diagnostika (Russian Clinical Laboratory Diagnostics). 2019; 64 (1): 53-56 (in Russ.).Disclosure of Interests:None declared

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.

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