scholarly journals Effects of Genomic Polymorphisms on the Course of Sepsis: Is There a Concept for Gene Therapy?

2001 ◽  
Vol 12 (suppl 1) ◽  
pp. S60-S64
Author(s):  
FRANK STÜBER
Keyword(s):  
Genetic Background ◽  
Inflammatory Responses ◽  
Interleukin 1 ◽  
Clinical Manifestations ◽  
Coagulation Factors ◽  
Multiple Organ ◽  
Genetic Determination ◽  
Wide Range ◽  
Genes Encoding ◽  
Anti Inflammatory

Abstract. Sepsis and its sequelae are still a major cause of morbidity and mortality on today's intensive care units. The evidence that endogenous mediators actually mediate the individual's response to infection has led to various approaches to assess the individual's contribution to the course of the disease. The role of an individual's genetic background and predisposition for the extent of inflammatory responses is determined by variabilities of genes encoding endogenous mediators that constitute the pathways of inflammation. Primary responses in inflammation are mediated by proinflammatory cytokines such as tumor necrosis factor and interleukin 1. Conversely, anti-inflammatory mediators are released and may induce a state of immunosuppression in sepsis. Pro- and anti-inflammatory responses contribute to the outcome of patients with systemic inflammation and sepsis. Therefore, all genes encoding proteins involved in the transduction of inflammatory processes are candidate genes to determine the human genetic background that is responsible for interindividual differences in systemic inflammatory responses to injury. The genetically determined capacity of cytokine production and release, heat shock protein expression, nitric oxide synthase activity, gene polymorphisms of coagulation factors or factors of the innate immune system-like defensins, and other genes involved in inflammation may contribute to a wide range of clinical manifestations of an inflammatory disease. Genomic information may be used to identify groups of patients with a high risk of developing severe sepsis and multiple organ dysfunction, and determining which patients will benefit from antimediator strategies because of their genetic determination to high cytokine release in the inflammatory response will be the subject of future trials.

scholarly journals Case of an unusual diagnosis of primary antiphospholipid syndrome with multiple clinical complications

2020 ◽  
Vol 2020 (12) ◽  
Author(s):  
Stathis Tsiakas ◽  
Chrysanthi Skalioti ◽  
Paraskevi Kotsi ◽  
Ioannis Boletis ◽  
Smaragdi Marinaki
Keyword(s):  
Antiphospholipid Syndrome ◽  
Thrombotic Event ◽  
Renal Involvement ◽  
Clinical Manifestations ◽  
Young Male ◽  
Multiple Organ ◽  
Systemic Autoimmune Disease ◽  
Antiphospholipid Antibody ◽  
Primary Antiphospholipid Syndrome ◽  
Wide Range

ABSTRACT Antiphospholipid syndrome (APS) is a systemic autoimmune disease defined by the presence of antiphospholipid antibodies in association with thrombotic events and/or obstetric complications. Renal involvement is not infrequent in both primary and secondary APS. Kidney manifestations comprise a wide range of clinical features, including hypertension, major renal vessel thrombosis or microvascular endothelial injury, also described as APS nephropathy. In the absence of a thrombotic event, clinical manifestations of APS are often non-specific. We recently encountered a case of primary APS in a young male with newly diagnosed hypertension and renal impairment. The diagnosis of APS was initially suspected by his kidney biopsy findings, when electron microscopy examination showed the features of chronic microangiopathy, and was later confirmed by a triple positive antiphospholipid antibody profile and multiple organ involvement.

Potential role of a series of lysine-/leucine-rich antimicrobial peptide in inhibiting lipopolysaccharide-induced inflammation

2018 ◽  
Vol 475 (22) ◽  
pp. 3687-3706 ◽  
Author(s):  
Weibing Dong ◽  
Xin Zhu ◽  
Xuan Zhou ◽  
Ying Yang ◽  
Xin Yan ◽  
...  
Keyword(s):  
Cell Membrane ◽  
Signaling Pathway ◽  
Inflammatory Responses ◽  
Antimicrobial Activities ◽  
Host Cells ◽  
Inflammatory Factors ◽  
Human Macrophage ◽  
U937 Cells ◽  
Wide Range ◽  
Anti Inflammatory

Antimicrobial peptides have broad-spectrum killing activities against bacteria, enveloped viruses, fungi and several parasites via cell membrane permeation and exhibit primarily immunomodulatory and anti-infective functions in their interactions with host cells. However, the mechanism underlying their anti-inflammatory activity remains to be elucidated. L-K6, an analog of temporin-1CEb isolated from the skin secretion of Rana chensinensis, has demonstrated a wide range of antimicrobial activities against gram-negative and gram-positive bacteria. In this study, the potent anti-inflammatory mechanism of L-K6 and its analogs in lipopolysaccharide (LPS)-stimulated human macrophage U937 cells were evaluated. We found that L-K6 suppressed the expression of inflammatory factors by two downstream signaling components in the MyD88-dependent pathway, including the mitogen-activated protein kinases (MAPKs) and the NF (nuclear factor)-κB signaling pathway, but its analog L-K5, which had the same amino acid sequence as L-K6 but no Lys residue at the –COOH terminal, only inhibited the phosphorylation of I-κB and NF-κB. Importantly, L-K6 and L-K5 were actively taken up by U937 cells through an independent cell membrane disruption mechanism and were eventually localized to the perinuclear region. The L-K6 uptake process was mediated by endocytosis, but L-K5 was specifically taken up by U937 cells via TLR4 endocytosis. Our results demonstrated that L-K6 can neutralize LPS and diassociate LPS micelles to inhibit LPS from triggering the proinflammatory signaling pathway, and by partially inhibiting inflammatory responses by the intracellular target. However, L-K5 may mainly inhibit proinflammatory responses by intracellular reporters to modulate the NF-κB signaling pathway.

scholarly journals Basal anti-inflammatory responses in cultured endothelial cells exposed to two conjugated linoleic acids

2020 ◽  
Vol 79 (OCE2) ◽  
Author(s):  
Carina Valenzuela ◽  
Elizabeth Miles ◽  
Philip Calder
Keyword(s):  
Inflammatory Responses ◽  
Adhesion Assay ◽  
Dependent Manner ◽  
Relative Expression ◽  
Inflammatory Pathways ◽  
Expression Of Genes ◽  
Low Concentrations ◽  
Genes Encoding ◽  
Anti Inflammatory ◽  
Pre Treatment

AbstractConjugated linoleic acid (CLA) isomers have been shown to possess anti-atherosclerotic properties, which may be related to the downregulation of inflammatory pathways. Whether low concentrations of CLAs are able to affect basal, unstimulated endothelial cell (EC) responses is not clear. The aim of this study was to evaluate the effects of two CLAs (cis-9, trans-11 and trans-10, cis-12) on basal inflammatory responses by ECs.EA.hy926 cells (HUVEC lineage) were cultured under standard conditions and exposed to CLAs (1 and 10 μM) for 48 hours. MTT assay was performed to determine cell viability; incorporation of FA was confirmed by gas chromatography; inflammatory mediators were assessed by multiplex immunoassay; the relative expression of genes encoding transcription factors and inflammatory cytokines was assessed through real-time PCR and static adhesion assay was used to evaluate monocyte attachment to the EC monolayer.CLAs were incorporated into ECs in a dose-dependent manner. Pre-treatment with CLA9,11 (1 uM) significantly reduced unstimulated, basal concentrations of MCP-1 (p < 0.05), and CLA10,12 at 10 uM had the same effect (p < 0.05). Both CLAs at 10 uM increased the relative expression of NFκβ (p < 0.01 and p < 0.05, respectively), while decreasing the relative expression of PPARα (p < 0.0001), COX-2 (p < 0.0001) and IL-6 (p < 0.0001). In contrast, no effect was observed in the adhesion assay for either CLA.These results suggest that both CLAs at a low concentration have a neutral or modest anti-inflammatory effect in basal conditions, which may influence endothelial function and risk of vascular disease. Interestingly, at these low CLA concentrations some pro-inflammatory genes are upregulated while others are down regulated. This suggests complex effects of CLAs on inflammatory pathways.

P1-312: Blocking interleukin-1 function attenuates Alzheimer's pathology via reducing anti-inflammatory responses in a transgenic mouse model

2010 ◽  
Vol 6 ◽  
pp. S264-S264
Author(s):  
Masashi Kitazawa ◽  
David Cheng ◽  
Michelle Tsukamoto ◽  
Vitaly Vasilevko ◽  
David C. Cribbs ◽  
...  
Keyword(s):  
Mouse Model ◽  
Transgenic Mouse ◽  
Inflammatory Responses ◽  
Interleukin 1 ◽  
Transgenic Mouse Model ◽  
Anti Inflammatory ◽  
Alzheimer’S Pathology

scholarly journals Biological and pathophysiological role of adiponectin

2019 ◽  
Vol 10 (2) ◽  
pp. 83-87
Author(s):  
Yury V. Petrenko ◽  
Ksenia S. Gerasimova ◽  
Valeria P. Novikova
Keyword(s):  
Adipose Tissue ◽  
Inflammatory Responses ◽  
Biological Activities ◽  
Normal Weight ◽  
Blood Levels ◽  
High Concentration ◽  
Obese People ◽  
Adipoq Gene ◽  
Wide Range ◽  
Anti Inflammatory

Adipose tissue is now recognized as an important endocrine organ that secretes numerous protein hormones, including leptin, adiponectin, and resistin. Adiponectin is a hormone that is produced by white adipose tissue. Adiponectin has been isolated independently by several groups of scientists. In humans, this protein is encoded by the ADIPOQ gene. Adiponectin receptors are widely distributed in many organs and tissues including liver, heart, pancreas, kidneys, muscles and many other cell types. A serum concentration of adipocin correlates with body mass index (BMI). Decreased level of adiponectin leads to obesity, the development of gestational complications in pregnant women, as well as a high risk of diabetes mellitus development and atherosclerosis. A high concentration of this hormone has anti-inflammatory, antiatherogenic, antiproliferative and cancer-defense mechanisms. Adiponectin strongly suppresses hepatic gluconeogenesis by inhibiting genes involved in glucose production. Obese people have lower blood levels of adiponectin than normal weight individuals. Adiponectin’s anti-inflammatory and anti-apoptotic properties result in protection of the blood vessels, heart, lungs, and colon. Adiponectin, an abundant adipocyte-secreted factor with a wide-range of biological activities, improves insulin sensitivity in insulin target tissues, modulates inflammatory responses, and plays a crucial role in the regulation of energy metabolism.

scholarly journals Children Living a Global Pandemic: Anxiety Repercussions

2021 ◽  
Author(s):  
Salvador I. Garcia-Adasme ◽  
Alejandro López-Escobar
Keyword(s):  
Physical Activity ◽  
Social Media ◽  
Clinical Manifestations ◽  
Multiple Organ ◽  
School Closures ◽  
Balanced Diet ◽  
Global Pandemic ◽  
Wide Range ◽  
Anxiety Levels ◽  
Children’S Anxiety

A global pandemic caused by SARS-CoV-2 is still beaten our world. The disease, termed COVID-19 by the WHO, has a wide range of clinical manifestations, ranging from a mild, self-limiting form of the disease to multiple organ failure and death, forcing governments to take measures to mitigate the transmission and reduce the economic impact. However, the paediatric manifestation appears to take a milder form of the disease but they are not oblivious to the consequences of the disease. They suffered personal and parental lost, broke their social relationships, forced to home confinement, school closures, all of them with secondary implications. As a result, children’s anxiety levels and manifestations have increased during pandemic. To prevent and counteract this situation, measures were implemented like increase physical activity, a balanced diet, and regular sleep pattern; and in relationship sphere use social media to stay in touch with school mates and relatives.

scholarly journals Efferocytosis potentiates the expression of arachidonate 15-lipoxygenase (ALOX15) in alternatively activated human macrophages through LXR activation

2020 ◽  
Author(s):  
Ryan G. Snodgrass ◽  
Yvonne Benatzy ◽  
Tobias Schmid ◽  
Dmitry Namgaladze ◽  
Malwina Mainka ◽  
...  
Keyword(s):  
Gene Expression ◽  
Tissue Repair ◽  
Cell Function ◽  
Immune Cell ◽  
Inflammatory Responses ◽  
Interleukin 1 ◽  
Th2 Cytokines ◽  
Alternatively Activated Macrophages ◽  
Anti Inflammatory ◽  
Alternatively Activated

Abstract Macrophages acquire anti-inflammatory and proresolving functions to facilitate resolution of inflammation and promote tissue repair. While alternatively activated macrophages (AAMs), also referred to as M2 macrophages, polarized by type 2 (Th2) cytokines IL-4 or IL-13 contribute to the suppression of inflammatory responses and play a pivotal role in wound healing, contemporaneous exposure to apoptotic cells (ACs) potentiates the expression of anti-inflammatory and tissue repair genes. Given that liver X receptors (LXRs), which coordinate sterol metabolism and immune cell function, play an essential role in the clearance of ACs, we investigated whether LXR activation following engulfment of ACs selectively potentiates the expression of Th2 cytokine-dependent genes in primary human AAMs. We show that AC uptake simultaneously upregulates LXR-dependent, but suppresses SREBP-2-dependent gene expression in macrophages, which are both prevented by inhibiting Niemann–Pick C1 (NPC1)-mediated sterol transport from lysosomes. Concurrently, macrophages accumulate sterol biosynthetic intermediates desmosterol, lathosterol, lanosterol, and dihydrolanosterol but not cholesterol-derived oxysterols. Using global transcriptome analysis, we identify anti-inflammatory and proresolving genes including interleukin-1 receptor antagonist (IL1RN) and arachidonate 15-lipoxygenase (ALOX15) whose expression are selectively potentiated in macrophages upon concomitant exposure to ACs or LXR agonist T0901317 (T09) and Th2 cytokines. We show priming macrophages via LXR activation enhances the cellular capacity to synthesize inflammation-suppressing specialized proresolving mediator (SPM) precursors 15-HETE and 17-HDHA as well as resolvin D5. Silencing LXRα and LXRβ in macrophages attenuates the potentiation of ALOX15 expression by concomitant stimulation of ACs or T09 and IL-13. Collectively, we identify a previously unrecognized mechanism of regulation whereby LXR integrates AC uptake to selectively shape Th2-dependent gene expression in AAMs.

scholarly journals The Dietary Flavonoid Kaempferol Mediates Anti-Inflammatory Responses via the Src, Syk, IRAK1, and IRAK4 Molecular Targets

2015 ◽  
Vol 2015 ◽  
pp. 1-15 ◽  
Author(s):  
Shi Hyoung Kim ◽  
Jae Gwang Park ◽  
Jongsung Lee ◽  
Woo Seok Yang ◽  
Gye Won Park ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Molecular Targets ◽  
Peritoneal Macrophages ◽  
Cellular Adhesion ◽  
Inflammatory Activity ◽  
Prostaglandin E ◽  
Genes Encoding ◽  
Anti Inflammatory

Even though a lot of reports have suggested the anti-inflammatory activity of kaempferol (KF) in macrophages, little is known about its exact anti-inflammatory mode of action and its immunopharmacological target molecules. In this study, we explored anti-inflammatory activity of KF in LPS-treated macrophages. In particular, molecular targets for KF action were identified by using biochemical and molecular biological analyses. KF suppressed the release of nitric oxide (NO) and prostaglandin E2(PGE2), downregulated the cellular adhesion of U937 cells to fibronectin (FN), neutralized the generation of radicals, and diminished mRNA expression levels of inflammatory genes encoding inducible NO synthase (iNOS), TNF-α, and cyclooxygenase- (COX-) 2 in lipopolysaccharide- (LPS-) and sodium nitroprusside- (SNP-) treated RAW264.7 cells and peritoneal macrophages. KF reduced NF-κB (p65 and p50) and AP-1 (c-Jun and c-Fos) levels in the nucleus and their transcriptional activity. Interestingly, it was found that Src, Syk, IRAK1, and IRAK4 responsible for NF-κB and AP-1 activation were identified as the direct molecular targets of KF by kinase enzyme assays and by measuring their phosphorylation patterns. KF was revealed to havein vitroandin vivoanti-inflammatory activity by the direct suppression of Src, Syk, IRAK1, and IRAK4, involved in the activation of NF-κB and AP-1.

scholarly journals Myxomavirus-Derived Serpin Prolongs Survival and Reduces Inflammation and Hemorrhage in an Unrelated Lethal Mouse Viral Infection

2013 ◽  
Vol 57 (9) ◽  
pp. 4114-4127 ◽  
Author(s):  
Hao Chen ◽  
Donghang Zheng ◽  
Jeff Abbott ◽  
Liying Liu ◽  
Mee Y. Bartee ◽  
...  
Keyword(s):  
Viral Infection ◽  
Serine Proteases ◽  
Viral Infections ◽  
Inflammatory Responses ◽  
Clotting Factor ◽  
Factor X ◽  
Virus Load ◽  
Murine Gammaherpesvirus ◽  
Wide Range ◽  
Anti Inflammatory

ABSTRACTLethal viral infections produce widespread inflammation with vascular leak, clotting, and bleeding (disseminated intravascular coagulation [DIC]), organ failure, and high mortality. Serine proteases in clot-forming (thrombotic) and clot-dissolving (thrombolytic) cascades are activated by an inflammatory cytokine storm and also can induce systemic inflammation with loss of normalserineproteaseinhibitor (serpin) regulation. Myxomavirus secretes a potent anti-inflammatory serpin, Serp-1, that inhibits clotting factor X (fX) and thrombolytic tissue- and urokinase-type plasminogen activators (tPA and uPA) with anti-inflammatory activity in multiple animal models. Purified serpin significantly improved survival in a murine gammaherpesvirus 68 (MHV68) infection in gamma interferon receptor (IFN-γR) knockout mice, a model for lethal inflammatory vasculitis. Treatment of MHV68-infected mice with neuroserpin, a mammalian serpin that inhibits only tPA and uPA, was ineffective. Serp-1 reduced virus load, lung hemorrhage, and aortic, lung, and colon inflammation in MHV68-infected mice and also reduced virus load. Neuroserpin suppressed a wide range of immune spleen cell responses after MHV68 infection, while Serp-1 selectively increased CD11c+splenocytes (macrophage and dendritic cells) and reduced CD11b+tissue macrophages. Serp-1 altered gene expression for coagulation and inflammatory responses, whereas neuroserpin did not. Serp-1 treatment was assessed in a second viral infection, mouse-adapted Zaire ebolavirus in wild-type BALB/c mice, with improved survival and reduced tissue necrosis. In summary, treatment with this unique myxomavirus-derived serpin suppresses systemic serine protease and innate immune responses caused by unrelated lethal viral infections (both RNA and DNA viruses), providing a potential new therapeutic approach for treatment of lethal viral sepsis.

scholarly journals Cytokine storms and pyroptosis are primarily responsible for the rapid death of mice infected with pseudorabies virus

2021 ◽  
Vol 8 (8) ◽  
pp. 210296
Author(s):  
Wei Sun ◽  
Shanshan Liu ◽  
Xuefei Huang ◽  
Rui Yuan ◽  
Jiansheng Yu
Keyword(s):  
Pseudorabies Virus ◽  
Immune Reaction ◽  
Inflammatory Responses ◽  
Interleukin 1 ◽  
Clinical Manifestations ◽  
Receptor Protein ◽  
Tnf Α ◽  
Pathogenesis Related ◽  
Hematoxylin Eosin ◽  
Pro Inflammatory Cytokines

Pseudorabies virus (PRV), the causative agent of Aujeszky's disease, is one of the most harmful pathogens to the pig industry. PRV can infect and kill a variety of mammals. Nevertheless, the underlying pathogenesis related to PRV is still unclear. This study aims to investigate the pathogenesis induced by PRV in a mouse model. The mice infected with the PRV-HLJ strain developed severe clinical manifestations at 36 h post-infection (hpi), and mortality occurred within 48–72 hpi. Hematoxylin-eosin staining and qRT-PCR methods were used to detect the pathological damage and expression of cytokines related to an immune reaction in brain tissue, respectively. The cytokine storms caused by IFN-α, IFN- β , TNF-α, IL-1 β , IL-6 and IL-18 were related to the histopathological changes induced by PRV. This pattern of cytokine secretion depicts an image of typical cytokine storms, characterized by dysregulated secretion of pro-inflammatory cytokines and imbalanced pro-inflammatory and anti-inflammatory responses. In addition, the pyroptosis pathway was also activated by PRV by elevating the expression levels of nod-like receptor protein 3, Caspase-1, Gasdermin-D and interleukin-1 β /18. These findings provide a way for further understanding the molecular basis in PRV pathogenesis.

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