Commentary on IL-1β associations with posttraumatic epilepsy development: A genetics and biomarker cohort study.
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ABSTRACT:
SUBMITTER: Rotenberg A
PROVIDER: S-EPMC4540220 | biostudies-literature | 2015 Jul
REPOSITORIES: biostudies-literature
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Commentary on IL-1β associations with posttraumatic epilepsy development: A genetics and biomarker cohort study.
Epilepsia 20150615 7
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Project description:ObjectivePosttraumatic epilepsy (PTE) is a significant complication following traumatic brain injury (TBI), yet the role of genetic variation in modulating PTE onset is unclear. We hypothesized that TBI-induced inflammation likely contributes to seizure development. We assessed whether genetic variation in the interleukin-1beta (IL-1β) gene, IL-1β levels in cerebrospinal fluid (CSF) and serum, and CSF/serum IL-1β ratios would predict PTE development post-TBI.MethodsWe investigated PTE development in 256 Caucasian adults with moderate-to-severe TBI. IL-1β tagging and functional single nucleotide polymorphisms (SNPs) were genotyped. Genetic variance and PTE development were assessed. Serum and CSF IL-1β levels were collected from a subset of subjects (n = 59) during the first week postinjury and evaluated for their associations with IL-1β gene variants, and also PTE. Temporally matched CSF/serum IL-1β ratios were also generated to reflect the relative contribution of serum IL-1β to CSF IL-1β.ResultsMultivariate analysis showed that higher CSF/serum IL-1β ratios were associated with increased risk for PTE over time (p = 0.008). Multivariate analysis for rs1143634 revealed an association between the CT genotype and increased PTE risk over time (p = 0.005). The CT genotype group also had lower serum IL-1β levels (p = 0.014) and higher IL-1β CSF/serum ratios (p = 0.093).SignificanceThis is the first report implicating IL-1β gene variability in PTE risk and linking (1) IL-1β gene variation with serum IL-1β levels observed after TBI and (2) IL-1β ratios with PTE risk. Given these findings, we propose that genetic and IL-1β ratio associations with PTE may be attributable to biologic variability with blood-brain barrier integrity during TBI recovery. These results provide a rationale for further studies (1) validating the impact of genetic variability on IL-1β production after TBI, (2) assessing genetically mediated signaling mechanisms that contribute to IL-1β CSF/serum associations with PTE, and (3) evaluating targeted IL-1β therapies that reduce PTE.
| S-EPMC4107119 | biostudies-literature
Project description:Epilepsy is a chronic disorder of the nervous system characterized by recurrent seizures. Inflammation is one of the six major causes of epilepsy, and its role in the pathogenesis of epilepsy is gaining increasing attention. Two signaling pathways, the high mobility group box-1 (HMGB1)/toll-like receptor 4 (TLR4) and interleukin-1β (IL-1β)/interleukin-1 receptor 1 (IL-1R1) pathways, have become the focus of research in recent years. These two signaling pathways have potential as biomarkers in the prediction, prognosis, and targeted therapy of epilepsy. This review focuses on the association between epilepsy and the neuroinflammatory responses mediated by these two signaling pathways. We hope to contribute further in-depth studies on the role of HMGB1/TLR4 and IL-1β/IL-1R1 signaling in epileptogenesis and provide insights into the development of specific agents targeting these two pathways.
| S-EPMC9274112 | biostudies-literature
Project description:BackgroundTo evaluate the relationship between IL-1α -889C/T (rs1800587), IL-1β -511C > T (rs16944), TNFα -308G > A (rs1800629), TNFα -238G > A (rs361525), IL-6 -174G > C (rs1800795), and IL-6 -572G > C (rs1800796) polymorphisms and the susceptibility to transposition of the great arteries (TGA).MethodsA prospective analysis was performed on mothers whose newborns were diagnosed as having TGA. For each case of TGA, a mother who gave birth to a healthy neonate in the same period was randomly selected for the control group. The sample size was calculated before planning the study with 80% power and 5% alpha.ResultsTwenty-seven mothers whose newborn had TGA anomalies (group 1) and 27 mothers whose newborn had no TGA (group 2) were included in the study. There were no significant differences between the groups in terms of maternal age, pregestational body mass index, gestational age at birth and infant sex (p > 0.05). The genotype and allele distributions of IL-1α -889C/T (rs1800587), IL-1β -511C > T (rs16944), TNFα -308G > A (rs1800629), TNFα -238G > A (rs361525), IL-6 -174G > C (rs1800795) and IL-6 -572G > C (rs1800796) gene variants were not different between the two groups (p > 0.05).ConclusionsThere was no relation between IL-1α, IL-1β, IL-6, and TNFα promoter gene polymorphisms and TGA occurrence in our study group.Trial registrationThis present prospective case-control study was conducted in Baskent University Hospital, Ankara, Turkey, between May 2020 and November 2021. Ethical approval was obtained from the university's Clinical Research Ethics Commitee (No: KA20/211) in accordance with the Declaration of Helsinki.
| S-EPMC9118748 | biostudies-literature
Project description: Not available
| S-EPMC9359298 | biostudies-literature
Project description:Interleukin-1β (IL-1β) is one of the most potent pro-inflammatory cytokines implicated in a wide range of autoinflammatory, autoimmune, infectious, and degenerative diseases. Therefore, many researchers have focused on developing therapeutic molecules that inhibit IL-1β-IL-1 receptor 1 (IL-1R1) interaction for the treatment of IL-1-related diseases. Among IL-1-related diseases, osteoarthritis (OA), is characterized by progressive cartilage destruction, chondrocyte inflammation, and extracellular matrix (ECM) degradation. Tannic acid (TA) has been proposed to have multiple beneficial effects, including anti-inflammatory, anti-oxidant, and anti-tumor activities. However, it is unclear whether TA plays a role in anti-IL-1β activity by blocking IL-1β-IL-1R1 interaction in OA. In this study, we report the anti-IL-1β activity of TA in the progression of OA in both in vitro human OA chondrocytes and in vivo rat OA models. Herein, using-ELISA-based screening, natural compound candidates capable of inhibiting the IL-1β-IL-1R1 interaction were identified. Among selected candidates, TA showed hindering IL-1β-IL-1R1 interaction by direct binding to IL-1β using surface plasmon resonance (SPR) assay. In addition, TA inhibited IL-1β bioactivity in HEK-Blue IL-1-dependent reporter cell line. TA also inhibited IL-1β-induced expression of inducible nitric oxide synthase (NOS2), cyclooxygenase-2 (COX-2), IL-6, tumor necrosis factor-alpha (TNF-α), nitric oxide (NO), and prostaglandin E2 (PGE2) in human OA chondrocytes. Moreover, TA downregulated IL-1β-stimulated matrix metalloproteinase (MMP)3, MMP13, ADAM metallopeptidase with thrombospondin type 1 motif (ADAMTS)4, and ADAMTS5, while upregulating collagen type II (COL2A1) and aggrecan (ACAN). Mechanistically, we confirmed that TA suppressed IL-1β-induced MAPK and NF-κB activation. The protective effects of TA were also observed in a monosodium iodoacetamide (MIA)-induced rat OA model by reducing pain and cartilage degradation and inhibiting IL-1β-mediated inflammation. Collectively, our results provide evidence that TA plays a potential role in OA and IL-1β-related diseases by hindering IL-1β-IL-1R1 interaction and suppressing IL-1β bioactivity.
| S-EPMC10118179 | biostudies-literature
Project description:Interleukin (IL)-4 and IL-13 were discovered approximately 30years ago and were immediately linked to allergy and atopic diseases. Since then, new roles for IL-4 and IL-13 and their receptors in normal gestation, fetal development and neurological function and in the pathogenesis of cancer and fibrosis have been appreciated. Studying IL-4/-13 and their receptors has revealed important clues about cytokine biology and led to the development of numerous experimental therapeutics. Here we aim to highlight new discoveries and consolidate concepts in the field of IL-4 and IL-13 structure, receptor regulation, signaling and experimental therapeutics.
| S-EPMC4546937 | biostudies-literature
Project description:p73 is a transcription factor belonging to the p53 tumour suppressor family. p73-/- mice exhibit a range of phenotypes including neurological, reproductive and inflammatory defects. Although the role of p73 in the control of genomic stability explains part of these phenotypes, a clear mechanism of how p73 participates in the inflammatory response is still elusive. Interleukin-1β (IL-1β) has a crucial role in mediating the inflammatory response. Because of its high potency to induce inflammation, the activation and secretion of IL-1β is tightly regulated by large protein complexes, named inflammasomes. Inflammasomes regulate activation of proinflammatory caspase-1, which in turn proteolytically processes its substrates, including pro-IL-1β. Caspase-1 gene transcription is strongly activated by p53 protein family members including p73. Here, we have addressed whether p73 might be directly involved in IL-1β regulation and therefore in the control of the inflammatory response. Our results show that TAp73β upregulates pro-IL-1β mRNA and processed IL-1β protein. In addition, analysis of breast and lung cancer patient cohorts demonstrated that interaction between p73 and IL-1β predicts a negative survival outcome in these human cancers.
| S-EPMC5243147 | biostudies-literature
Project description:BackgroundWhile life-long impacts exist for infants born one or two weeks early little evidence exists for those infants born after their due date. However interventions could be used to expedite birth if the risks of continuing the pregnancy are higher than intervening. It is known that the risk of epilepsy in childhood is higher in infants exposed to perinatal compromise and therefore may be useful as a proxy for intrapartum compromise. The aim of this work is to quantify the likelihood of children developing epilepsy based on their gestational age at birth (37-39 weeks or ≥41 weeks).MethodsThe work is based on term infants born in Sweden between 1983 and 1993 (n = 1,030,168), linked to data on disability pension, child mortality and in-patient epilepsy care. The reference group was defined as infants born at 39 or 40 completed weeks of gestation; compared with infants born at early term (37/38 weeks) or late/post term (41 weeks or more). Primary outcome was defined a-priori as a diagnosis of epilepsy before 20 years of age. Secondary outcomes were childhood mortality (before five years of age), and registered for disability pension before 20 years of age. Logistic regression models were used to assess any association of the outcomes with gestational age at birth.FindingsIn the unadjusted results, infants born 7 or more days after their due date had higher risks of epilepsy and disability pension than the reference group, but similar risks of child death. Early term infants showed higher risks of epilepsy, disability pension and child death. After adjustment for confounders, there remained a higher risk of epilepsy for both early term (OR 1·19 (1·11-1·29)) and late/post term infants (OR 1·13 (1·06-1·22)).InterpretationInfants born at 37/38 week or 41 weeks and above, when compared to those born at 39 or 40 weeks gestation, have an increased risk of developing epilepsy. This data could be useful in helping women and care givers make decisions with regard to the timing of induction of labour.
| S-EPMC6312375 | biostudies-literature