Role of p38 MAPK and pro‐inflammatory cytokines expression in glutamate‐induced neuronal death of neonatal rats

2008 ◽  
Vol 26 (5) ◽  
pp. 487-495 ◽  
Author(s):  
V. Chaparro‐Huerta ◽  
M.E. Flores‐Soto ◽  
G. Gudiño‐Cabrera ◽  
M.C. Rivera‐Cervantes ◽  
O.K. Bitzer‐Quintero ◽  
...  
Keyword(s):  
P38 Mapk ◽  
Inflammatory Cytokines ◽  
Neuronal Death ◽  
Neonatal Rats ◽  
Pro Inflammatory Cytokines

scholarly journals The Role of Toll-like receptor 4 in respiratory syncytial virus replication, interferon lambda 1 induction, and chemokine responses

2018 ◽  
Author(s):  
Lindsay Broadbent ◽  
Jonathon D. Coey ◽  
Michael D. Shields ◽  
Ultan F. Power
Keyword(s):  
Respiratory Syncytial Virus ◽  
Immune Responses ◽  
P38 Mapk ◽  
Inflammatory Cytokines ◽  
Virus Replication ◽  
Growth Kinetics ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
Pro Inflammatory Cytokines

AbstractRespiratory syncytial virus (RSV) infection is the leading cause of severe lower respiratory tract infections (LRTI) in infants worldwide. The immune responses to RSV infection are implicated in RSV pathogenesis but RSV immunopathogenesis in humans remains poorly understood. We previously demonstrated that IFN-λ1 is the principle interferon induced following RSV infection of infants and well-differentiated primary pediatric bronchial epithelial cells (WD-PBECs). Interestingly, RSV F interacts with the TLR4/CD14/MD2 complex to initiate secretion of pro-inflammatory cytokines, while TLR4 stimulation with house dust mite induces IFN-λ1 production. However, the role of TLR4 in RSV infection and concomitant IFN-λ1 induction remains unclear. Using our RSV/WD-PBEC infection model, we found that CLI-095 inhibition of TLR4 resulted in significantly reduced viral growth kinetics, and secretion of IFN-λ1 and pro-inflammatory chemokines. To elucidate specific TLR4 signalling intermediates implicated in virus replication and innate immune responses we selected 4 inhibitors, including LY294002, U0126, SB203580 and JSH-23. SB203580, a p38 MAPK inhibitor, reduced both viral growth kinetics and IFN-λ1 secretion, while JSH-23, an NF-κB inhibitor, reduced IFN-λ1 secretion without affecting virus growth kinetics. Our data indicate that TLR4 plays a role in RSV entry and/or replication and IFN-λ1 induction following RSV infection is mediated, in part, by TLR4 signalling through NF- κB and/or p38 MAPK. Therefore, targeting TLR4 or downstream effector proteins could present novel treatment strategies against RSV.ImportanceThe role of TLR4 in RSV infection and IFN-λ1 induction is controversial. Using our WD-PBEC model, which replicates many hallmarks of RSV infection in vivo, we demonstrated that the TLR4 pathway is involved in both RSV infection and/or replication and the concomitant induction of IFN-λ1 and other pro-inflammatory cytokines. Increasing our understanding of the role of TLR4 in RSV immunopathogenesis may lead to the development of novel RSV therapeutics.

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 Computational Identification of Potential Anti-Inflammatory Natural Compounds Targeting the p38 Mitogen-Activated Protein Kinase (MAPK): Implications for COVID-19-Induced Cytokine Storm

Biomolecules ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 653
Author(s):  
Seth O. Asiedu ◽  
Samuel K. Kwofie ◽  
Emmanuel Broni ◽  
Michael D. Wilson
Keyword(s):  
Molecular Docking ◽  
P38 Mapk ◽  
Inflammatory Cytokines ◽  
Binding Energies ◽  
Mitogen Activated Protein Kinase ◽  
Inflammatory Activity ◽  
Computational Techniques ◽  
Cytokine Storm ◽  
Anti Inflammatory ◽  
Pro Inflammatory Cytokines

Severely ill coronavirus disease 2019 (COVID-19) patients show elevated concentrations of pro-inflammatory cytokines, a situation commonly known as a cytokine storm. The p38 MAPK receptor is considered a plausible therapeutic target because of its involvement in the platelet activation processes leading to inflammation. This study aimed to identify potential natural product-derived inhibitory molecules against the p38α MAPK receptor to mitigate the eliciting of pro-inflammatory cytokines using computational techniques. The 3D X-ray structure of the receptor with PDB ID 3ZS5 was energy minimized using GROMACS and used for molecular docking via AutoDock Vina. The molecular docking was validated with an acceptable area under the curve (AUC) of 0.704, which was computed from the receiver operating characteristic (ROC) curve. A compendium of 38,271 natural products originating from Africa and China together with eleven known p38 MAPK inhibitors were screened against the receptor. Four potential lead compounds ZINC1691180, ZINC5519433, ZINC4520996 and ZINC5733756 were identified. The compounds formed strong intermolecular bonds with critical residues Val38, Ala51, Lys53, Thr106, Leu108, Met109 and Phe169. Additionally, they exhibited appreciably low binding energies which were corroborated via molecular mechanics Poisson–Boltzmann surface area (MM-PBSA) calculations. The compounds were also predicted to have plausible pharmacological profiles with insignificant toxicity. The molecules were also predicted to be anti-inflammatory, kinase inhibitors, antiviral, platelet aggregation inhibitors, and immunosuppressive, with probable activity (Pa) greater than probable inactivity (Pi). ZINC5733756 is structurally similar to estradiol with a Tanimoto coefficient value of 0.73, which exhibits anti-inflammatory activity by targeting the activation of Nrf2. Similarly, ZINC1691180 has been reported to elicit anti-inflammatory activity in vitro. The compounds may serve as scaffolds for the design of potential biotherapeutic molecules against the cytokine storm associated with COVID-19.

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

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