scholarly journals Inflammatory aspects of epileptogenesis: contribution of molecular inflammatory mechanisms

2016 ◽  
Vol 29 (1) ◽  
pp. 1-16 ◽  
Author(s):  
Feyza Alyu ◽  
Miriş Dikmen
Keyword(s):  
Interleukin 1 ◽  
Mammalian Target Of Rapamycin ◽  
Signalling Pathways ◽  
Pharmacological Agents ◽  
Inflammatory Protein ◽  
Pubmed Database ◽  
Inflammatory Processes ◽  
Inflammatory Proteins ◽  
Genetically Determined

ObjectiveEpilepsy is a chronic neurological disease characterised with seizures. The aetiology of the most generalised epilepsies cannot be explicitly determined and the seizures are pronounced to be genetically determined by disturbances of receptors in central nervous system. Besides, neurotransmitter distributions or other metabolic problems are supposed to involve in epileptogenesis. Lack of adequate data about pharmacological agents that have antiepileptogenic effects point to need of research on this field. Thus, in this review, inflammatory aspects of epileptogenesis has been focussed via considering several concepts like role of immune system, blood–brain barrier and antibody involvement in epileptogenesis.MethodsWe conducted an evidence-based review of the literatures in order to evaluate the possible participation of inflammatory processes to epileptogenesis and also, promising agents which are effective to these processes. We searched PubMed database up to November 2015 with no date restrictions.ResultsIn the present review, 163 appropriate articles were included. Obtained data suggests that inflammatory processes participate to epileptogenesis in several ways like affecting fibroblast growth factor-2 and tropomyosin receptor kinase B signalling pathways, detrimental proinflammatory pathways [such as the interleukin-1 beta (IL-1β)–interleukin-1 receptor type 1 (IL-1R1) system], mammalian target of rapamycin pathway, microglial activities, release of glial inflammatory proteins (such as macrophage inflammatory protein, interleukin 6, C–C motif ligand 2 and IL-1β), adhesion molecules that are suggested to function in signalling pathways between neurons and microglia and also linkage between these molecules and proinflammatory cytokines.ConclusionThe literature research indicated that inflammation is a part of epileptogenesis. For this reason, further studies are necessary for assessing agents that will be effective in clinical use for therapeutic treatment of epileptogenesis.

Phosphoinositide 3-kinases and their role in inflammation: potential clinical targets in atherosclerosis?

2009 ◽  
Vol 116 (11) ◽  
pp. 791-804 ◽  
Author(s):  
Anne Fougerat ◽  
Stéphanie Gayral ◽  
Nicole Malet ◽  
Fabienne Briand-Mesange ◽  
Monique Breton-Douillon ◽  
...  
Keyword(s):  
Inflammatory Cell ◽  
Signalling Pathways ◽  
Cell Recruitment ◽  
Intracellular Signalling Pathways ◽  
Inflammatory Processes ◽  
Inflammatory Proteins ◽  
Inflammatory Cell Recruitment ◽  
Phosphoinositide 3 Kinase ◽  
Innovative Drugs

Inflammation has a central role in the pathogenesis of atherosclerosis at various stages of the disease. Therefore it appears of great interest to develop novel and innovative drugs targeting inflammatory proteins for the treatment of atherosclerosis. The PI3K (phosphoinositide 3-kinase) family, which catalyses the phosphorylation of the 3-OH position of phosphoinositides and generates phospholipids, controls a wide variety of intracellular signalling pathways. Recent studies provide evidence for a crucial role of this family not only in immune function, such as inflammatory cell recruitment, and expression and activation of inflammatory mediators, but also in antigen-dependent responses making it an interesting target to modulate inflammatory processes. The present review will focus on the regulation of inflammation within the vasculature during atherogenesis. We will concentrate on the different functions played by each isoform of PI3K in immune cells which could be involved in this pathology, raising the possibility that inhibition of one or more PI3K isoforms may represent an effective approach in the treatment of atherosclerosis.

scholarly journals Evidence-Based Management of Gout - A Systematic Search and Review

2020 ◽  
Author(s):  
Md Abu Bakar Siddiq
Keyword(s):  
Risk Factors ◽  
Treatment Options ◽  
Evidence Based ◽  
Level Of Evidence ◽  
Pharmacological Agents ◽  
New Synthesis ◽  
Pubmed Database ◽  
Anti Inflammatory ◽  
Clinical Conditions

Gout is the most common form of inflammatory arthritis. Hyperuricaemia is the pre-requisite for gout and is influenced by variable modifiable and non-modifiable risk factors. Clinical features unique for gout are due to deposition of monosodium urate (MSU) crystal in articular and extra articular tissues. Among various treating agents, anti-inflammatory drugs and urate lowering therapies (ULT) are used widely and successfully, however, non-medicinal means are also effective in the disorder. In their updated guidelines, ACR (2012) and EULAR (2016) recommended both medicinal and non-medicinal approaches that could be used in treating gout, though some of the recommendations are based on lower level of evidence. Moreover, researchers’ continued effort in finding new gout managing agents appear promising, for example, role of Lesinurad in gout management (CLEAR1, CLEAR2). In this new synthesis the author is aimed to provide updated information on gout management based on a systematic review including published work within last ten years between 2008 and 2018 and for this purpose, using ‘clinical trials in gout management’ string, published worked searched in PubMed database from 1st September 2018 to 30 October 2018. Besides the recent ACR and EULAR evidence based management guidelines, the author reviewed another 91 (total 93) articles to make this new draft – 39 articles describe role of pharmacological agents and 54 describe different gout risks, pharmacokinetics/pharmacodynamics of ULT, association between raised sUA level and renal impairment, efficacy of non-pharmacological agents in reducing sUA. According to published work, anti-inflammatory agent is the most appropriate drug group in mitigating inflammatory symptoms of gout, though they often adversely affect over other vital 2 organs with impaired function. Besides ULT, uricase analogues are also found useful in non refractory gout. Since anti-inflammatory agents and ULT contraindicate in some clinical conditions, intra-articular steroid and or adrenocorticotropic hormone (ACTH) are appropriate alternatives instead. However, head-to-head comparison between different NSAIDs, NSAID and prednisolone, NSAID and colchicine are yet to perform. Use of combined anti-inflammatory preparations in gout is also based on lower level of evidence. Regarding effective maximum dose and long-standing impact of ULT on vital organs we are yet to reach a conclusion. Likewise, non-medicinal approaches are widely using in achieving target sUA level, though some of them are based on biased study outcomes and or study with inadequate power, requiring further analysis. Among non-pharmacological approaches, life-style modification, restriction of purine rich diets, avoidance of gout inciting agents are important, but inconclusive. Educating patients’ about diseases, risk factors, available treatment options and side effects from them are also important in terms of achieving sUA level, nevertheless too much counseling sometimes could be worthless.

scholarly journals Targeting the interleukin-1 pathway in patients with hematological disorders

Blood ◽  
2017 ◽  
Vol 129 (24) ◽  
pp. 3155-3164 ◽  
Author(s):  
Charlotte E. M. de Mooij ◽  
Mihai G. Netea ◽  
Walter J. F. M. van der Velden ◽  
Nicole M. A. Blijlevens
Keyword(s):  
Animal Studies ◽  
Hematological Malignancies ◽  
Inflammatory Diseases ◽  
Interleukin 1 ◽  
Hematological Disorders ◽  
Graft Versus Host ◽  
Inflammatory Processes ◽  
Intestinal Mucositis ◽  
Interleukin 1Α

Abstract Interleukin-1α (IL-1α) and IL-1β are potent inflammatory cytokines that activate local and systemic inflammatory processes and are involved in protective immune responses against infections. However, their dysregulated production and signaling can aggravate tissue damage during infection, inflammatory diseases, and chemotherapy-induced intestinal mucositis. Additionally, cytokines of the IL-1 family play an important role in homeostatic as well as “emergency” hematopoiesis and are involved in the pathogenesis of several myeloid and lymphoid hematological malignancies. In the pathogenesis of intestinal mucositis and graft-versus-host disease (GVHD), these cytokines are considered pivotal during the initiation as well as propagation phase, and insights from animal studies suggest that targeting the IL-1 pathway can significantly ameliorate mucositis and GVHD. Moreover, IL-1α and IL-1β might prove to be valuable targets for both prevention and treatment of cancer and cancer therapy–related complications, and the first clinical studies have already been performed in the setting of hematological malignancies. In this review, we will discuss the role of cytokines of the IL-1 family in hematological malignancies, chemotherapy-induced intestinal mucositis, and GVHD, and speculate on possibilities of therapeutically targeting the IL-1 pathway in hematological patients.

scholarly journals Alpha 1-Antichymotrypsin, an Inflammatory Protein Overexpressed in the Brains of Patients with Alzheimer’s Disease, Induces Tau Hyperphosphorylation through c-Jun N-Terminal Kinase Activation

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Ethika Tyagi ◽  
Tina Fiorelli ◽  
Michelle Norden ◽  
Jaya Padmanabhan
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Interleukin 1 ◽  
Tau Phosphorylation ◽  
Primary Neurons ◽  
Tau Hyperphosphorylation ◽  
Kinase Activation ◽  
Inflammatory Protein ◽  
Jnk Inhibitors ◽  
Inflammatory Proteins

The association of inflammatory proteins with neuritic plaques in the brains of Alzheimer’s disease (AD) patients has led to the hypothesis that inflammation plays a pivotal role in the development of pathology in AD. Earlier studies have shown that alpha 1-antichymotrypsin (ACT) enhances amyloid beta fibrillization and accelerated plaque formation in APP transgenic mice. Later studies from our laboratory have shown that purified ACT induces tau hyperphosphorylation and degeneration in neurons. In order to understand the mechanisms by which inflammatory proteins enhance tau hyperphosphorylation, we injected interleukin-1β(IL-1β) intracerebroventricularly into mice expressing human ACT, human tau, or both transgenes. It was found that the hyperphosphorylation of tau in ACT and ACT/htau mice after IL-1βinjection correlated with increased phosphorylation of c-Jun N-terminal kinase (JNK). We verified the involvement of JNK in ACT-induced tau phosphorylation by utilizing JNK inhibitors in cultured primary neurons treated with ACT, and we found that the inhibitor showed complete prevention of ACT-induced tau phosphorylation. These results indicate that JNK is one of the major kinases involved in the ACT-mediated tau hyperphosphorylation and suggest that inhibitors of this kinase may protect against inflammation-induced tau hyperphosphorylation and neurodegeneration associated with AD.

scholarly journals Emerging role of interleukin-1 in cardiovascular diseases

2009 ◽  
pp. 481-498
Author(s):  
B Vicenová ◽  
V Vopálenský ◽  
L Burýšek ◽  
M Pospíšek
Keyword(s):  
Rheumatoid Arthritis ◽  
Diabetes Mellitus ◽  
Cardiovascular Diseases ◽  
Cardiovascular Events ◽  
Current Knowledge ◽  
Interleukin 1 ◽  
Proinflammatory Mediators ◽  
Inflammatory Processes ◽  
Higher Eukaryotes

There is an increasing evidence linking dysbalance between various proinflammatory mediators and higher risk of cardiovascular events and pathologies. Likewise, some of the cardiovascular diseases lately appeared to have an autoimmune component. Interleukin-1 (IL-1), a master regulator of diverse inflammatory processes in higher eukaryotes and the key player in numerous autoimmune disorders including rheumatoid arthritis, diabetes mellitus or systemic sclerosis, has recently been proved to be involved in development of several cardiovascular diseases as well. This report aims to give a summary on current knowledge about the IL-1 signaling pathways and about the implication of IL-1 and the IL-1 receptor antagonist (IL-1Ra) in some of the diseases of the cardiovascular system.

scholarly journals Wnt/β-catenin signaling as a useful therapeutic target in hepatoblastoma

2019 ◽  
Vol 39 (9) ◽  
Author(s):  
Ying-Li Sha ◽  
Shuang Liu ◽  
Wen-Wen Yan ◽  
Bo Dong
Keyword(s):  
Signaling Pathways ◽  
Target Genes ◽  
Mammalian Target Of Rapamycin ◽  
Growth Factor Receptor ◽  
Pharmacological Agents ◽  
Ample Evidence ◽  
Diagnosis And Prognosis ◽  
Neurokinin 1 ◽  
Factor Α

Abstract Hepatoblastoma is a malignant tumor in the liver of children that generally occurs at the age of 2–3 years. There have been ample evidence from the preclinical as well as clinical studies suggesting the activation of Wnt/β-catenin signaling in hepatoblastoma, which is mainly attributed to the somatic mutations in the exon 3 of β-catenin gene. There is increased translocation of β-catenin protein from the cell surface to cytoplasm and nucleus and intracellular accumulation is directly linked to the severity of the cancer. Accordingly, the alterations in β-catenin and its target genes may be used as markers in the diagnosis and prognosis of pediatric live tumors. Furthermore, scientists have reported the therapeutic usefulness of inhibition of Wnt/β-catenin signaling in hepatoblastoma and this inhibition of signaling has been done using different methods including short interfering RNA (siRNA), miRNA and pharmacological agents. Wnt/β-catenin works in association with other signaling pathways to induce the development of hepatoblastoma including Yes-associated protein (YAP)1 (YAP-1), mammalian target of rapamycin (mTOR) 1 (mTOR-1), SLC38A1, glypican 3 (GPC3), nuclear factor κ-light-chain-enhancer of activated B cells (NF-kB), epidermal growth factor receptor, ERK1/2, tumor necrosis factor-α (TNF-α), regenerating islet-derived 1 and 3 α (REG1A and 3A), substance P (SP)/neurokinin-1 receptor and PARP-1. The present review describes the key role of Wnt/β-catenin signaling in the development of hepatoblastoma. Moreover, the role of other signaling pathways in hepatoblastoma in association with Wnt/β-catenin has also been described.

scholarly journals The lysosome: a crucial hub for AMPK and mTORC1 signalling

2017 ◽  
Vol 474 (9) ◽  
pp. 1453-1466 ◽  
Author(s):  
Bernadette Carroll ◽  
Elaine A. Dunlop
Keyword(s):  
Amino Acid ◽  
Mammalian Target Of Rapamycin ◽  
Signalling Pathways ◽  
Initial Discovery ◽  
Multiple Levels ◽  
Energy Sensing ◽  
Amino Acid Sensing ◽  
Amp Activated Protein Kinase ◽  
Mtorc1 Activation

Much attention has recently been focussed on the lysosome as a signalling hub. Following the initial discovery that localisation of the nutrient-sensitive kinase, mammalian target of rapamycin complex 1 (mTORC1), to the lysosome was essential for mTORC1 activation, the field has rapidly expanded to reveal the role of the lysosome as a platform permitting the co-ordination of several homeostatic signalling pathways. Much is now understood about how the lysosome contributes to amino acid sensing by mTORC1, the involvement of the energy-sensing kinase, AMP-activated protein kinase (AMPK), at the lysosome and how both AMPK and mTORC1 signalling pathways feedback to lysosomal biogenesis and regeneration following autophagy. This review will cover the classical role of the lysosome in autophagy, the dynamic signalling interactions which take place on the lysosomal surface and the multiple levels of cross-talk which exist between lysosomes, AMPK and mTORC1.

Role of interleukin-1 in the pulmonary immune response duringPseudomonas aeruginosapneumonia

2002 ◽  
Vol 282 (2) ◽  
pp. L285-L290 ◽  
Author(s):  
Marc J. Schultz ◽  
Anita W. Rijneveld ◽  
Sandrine Florquin ◽  
Carl K. Edwards ◽  
Charles A. Dinarello ◽  
...  
Keyword(s):  
Pulmonary Infection ◽  
Interleukin 1 ◽  
Wild Type ◽  
Inflammatory Protein ◽  
Colony Forming Units ◽  
Factor Α ◽  
Macrophage Inflammatory Protein ◽  
Necrosis Factor

Pneumonia is associated with elevated concentrations of the proinflammatory cytokine interleukin (IL)-1 in the pulmonary compartment. To study the role of IL-1 in the pathogenesis of Pseudomonas pneumonia, IL-1 receptor type 1 gene-deficient ( IL-1R −/−) mice and wild-type mice were intranasally inoculated with Pseudomonas aeruginosa. The absence of the IL-1 signal attenuated the outgrowth of Pseudomonas in lungs, as reflected by an increasing number of colony-forming units (cfu) during Pseudomonaspneumonia in wild-type mice and a concurrently decreasing number of cfu during pulmonary infection in IL-1R −/− mice ( P < 0.05, IL-1R −/− mice vs. wild-type mice). Influx of neutrophils was decreased in bronchoalveolar lavage fluids in IL-1R −/− mice compared with wild-type mice. Similarly, lung levels of cytokines (tumor necrosis factor-α, IL-6) and chemokines (macrophage inflammatory protein-2 and KC) were lower in IL-1R −/− mice 24 h postinoculation. Consistent with results obtained in IL-1R −/− mice, treatment of wild-type mice with IL-1R antagonist also diminished outgrowth of Pseudomonas when compared with wild-type mice treated with vehicle ( P < 0.05). These results demonstrate that an absence or reduction in endogenous IL-1 activity improves host defense against Pseudomonas pneumonia while suppressing the inflammatory response.

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