IL-1β is a key cytokine that induces trypsin upregulation in the influenza virus-cytokine-trypsin cycle.
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ABSTRACT:
SUBMITTER: Indalao IL
PROVIDER: S-EPMC5225228 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Febrile seizures (FSs) are the most common convulsions in childhood. Studies have demonstrated a significant relationship between a history of prolonged FSs during early childhood and temporal sclerosis, which is responsible for intractable mesial temporal lobe epilepsy. It has been shown that interleukin-1β (IL-1β) is intrinsically involved in the febrile response in children and in the generation of FSs. We summarize the gene polymorphisms, changes of IL-1β levels and the putative role of IL-1β in the generation of FSs. IL-1β could play a role either in enhancing or in reducing neural excitability. If the enhancing and reducing effects are balanced, an FS does not occur. When the enhancing effect plays the leading role, an FS is generated. A mild imbalance can cause simple FSs while a severe imbalance can cause complex FSs and febrile status epilepticus. Therefore, anti-IL-1β therapy may help to treat FSs.
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Project description:The influenza A virus (IAV) H1N1pdm09 induces exacerbated inflammation, contributing to disease complications. Inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α), favor an inflammatory response that aids viral replication and survival. A pathway by which spontaneous TNF-α production occurs involves either the reduction of Siglec-3 (CD33) levels or the absence of its ligand, sialic acid. Influenza virus uses sialic acid to enter cells by reducing their expression; however, the role of CD33 in IAV H1N1pdm09 stimulation and its relationship with inflammation have not yet been studied. To evaluate the role of CD33 in proinflammatory cytokine production in IAV H1N1pdm09 stimulation, peripheral blood mononuclear cells from healthy subjects were incubated with IAV H1N1pdm09. We observed that the infection caused an increase in the mRNA expression of proinflammatory cytokines such as TNF-α, interleukin (IL)-1β, and IL-6 and a significant reduction in CD33 expression by monocytes at an early stage of infection. Additionally, suppressor of cytokine signaling 3 (SOCS-3) mRNA expression was upregulated at 6 h, and reactive oxygen species (ROS) production increased at 1.5 h. Moreover, a significant reduction in CD33 expression on the cell surface of monocytes from influenza patients or of IAV H1N1pdm09-stimulated monocytes incubated in vitro was observed by flow cytometry. The results suggest that the decrease in CD33 and increase of SOCS-3 expression induced by IAV H1N1pdm09 triggered TNF-α secretion and ROS production, suggesting an additional way to exacerbate inflammation during viral infection.
| S-EPMC8882749 | biostudies-literature
Project description:Peroxisome proliferator-activated receptors (PPARs) are a family of nuclear hormone receptors. In skin, PPARs modulate inflammation, lipid synthesis, keratinocyte differentiation and proliferation and thus are important for skin barrier homeostasis. Accordingly, PPAR expression is altered in various skin conditions that entail epidermal barrier impairment, that is atopic dermatitis (AD) and psoriasis. Using human epidermal equivalents (HEEs), we established models of acute epidermal barrier impairment devoid of immune cells. We assessed PPAR and cytokine expression after barrier perturbation and examined effects of keratinocyte-derived cytokines on PPAR expression. We show that acetone or SDS treatment causes graded impairment of epidermal barrier function. Furthermore, we demonstrate that besides IL-1β and TNFα, IL-33 and TSLP are highly relevant markers for acute epidermal barrier impairment. Both SDS- and acetone-mediated epidermal barrier impairment reduce PPARG expression levels, whereas only SDS enhances PPARD expression. In line with findings in IL-1β and TNFα-treated HEEs, abrogation of IL-1 signalling restores PPARG expression and limits the increase of PPARD expression in SDS-induced epidermal barrier impairment. Thus, following epidermal barrier perturbation, keratinocyte-derived IL-1β and partly TNFα modulate PPARG and PPARD expression. These results emphasize a role for PPARγ and PPARβ/δ in acute epidermal barrier impairment with possible implications for diseases such as AD and psoriasis.
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Project description:Mycetoma is a neglected tropical disease, endemic in many tropical and subtropical regions, characterised by massive deformity and disability and can be fatal if untreated early and appropriately. Interleukins (IL) -35 and IL-37 are newly discovered cytokines that play an important role in suppressing the immune system. However, the expression of these interleukins in patients with Madurella mycetomatis (M. mycetomatis) induced eumycetoma has not yet been explored. The aim of this study is to determine the levels of IL-1 family (IL-1β, IL-37) and IL-12 family (IL-12, IL-35) in a group of these patients and the association between these cytokines levels and the patients' demographic characteristics. The present, case-control study was conducted at the Mycetoma Research Centre, Soba University Hospital, University of Khartoum, Sudan and it included 140 individuals. They were divided into two groups; group I: healthy controls [n = 70; median age 25 years (range 12 to 70 years)]. Group II: mycetoma patients [n = 70 patients; median age 25 (range 13 to 70 years)]. Cytokines levels were measured in sera using enzyme linked immunosorbent assay (ELISA). There was a significant negative correlation between IL-1β and IL-12 levels and lesion size and disease duration, while IL-37 and IL-35 levels were significantly positively correlated with both lesion size and disease duration. The analysis of the risk factors of higher circulatory levels of IL-37 in patients of mycetoma showed a negative significant association with IL-1β cytokine, where a unit increment in IL-1β will decrease the levels of IL-37 by 35.28 pg/ml. The levels of IL-37 among the patients with a duration of mycetoma infection ≤ 1 year were significantly low by an average of 18.45 pg/ml compared to patients with a mycetoma infection's duration of ≥ 5years (reference group). Furthermore, the risk factors of higher levels of IL-35 in mycetoma patients revealed a negative significant association with IL-12, as a unit increment in IL-12 decreases the levels of IL-35 by 8.99 pg/ml (p < 0.001). Levels of IL-35 among the patients with duration of mycetoma infection ≤ one year were significantly low on average by 41.82 pg/ml (p value = 0.002) compared to patients with a duration of mycetoma infection ≥ 5 years (reference group). In conclusion, this study indicates that both IL-35 and IL-37 are negatively associated with the levels of IL-1β and IL-12 in eumycetoma mycetoma infection; and high levels of IL-37 and IL-35 may have a negative impact on disease progression.
| S-EPMC6483278 | biostudies-literature
Project description:Cystic fibrosis (CF) lung disease is characterized by early and persistent mucus accumulation and neutrophilic inflammation in the distal airways. Identification of the factors in CF mucopurulent secretions that perpetuate CF mucoinflammation may provide strategies for novel CF pharmacotherapies. We show that IL-1β, with IL-1α, dominated the mucin prosecretory activities of supernatants of airway mucopurulent secretions (SAMS). Like SAMS, IL-1β alone induced MUC5B and MUC5AC protein secretion and mucus hyperconcentration in CF human bronchial epithelial (HBE) cells. Mechanistically, IL-1β induced the sterile α motif-pointed domain containing ETS transcription factor (SPDEF) and downstream endoplasmic reticulum to nucleus signaling 2 (ERN2) to upregulate mucin gene expression. Increased mRNA levels of IL1B, SPDEF, and ERN2 were associated with increased MUC5B and MUC5AC expression in the distal airways of excised CF lungs. Administration of an IL-1 receptor antagonist (IL-1Ra) blocked SAMS-induced expression of mucins and proinflammatory mediators in CF HBE cells. In conclusion, IL-1α and IL-1β are upstream components of a signaling pathway, including IL-1R1 and downstream SPDEF and ERN2, that generate a positive feedback cycle capable of producing persistent mucus hyperconcentration and IL-1α and/or IL-1β-mediated neutrophilic inflammation in the absence of infection in CF airways. Targeting this pathway therapeutically may ameliorate mucus obstruction and inflammation-induced structural damage in young CF children.
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Project description:Secondary methicillin-resistant Staphylococcus aureus (MRSA) infection is a cause of severe pneumonia with high mortality during influenza A virus (IAV) pandemics. Alveolar macrophages (AMs) mount cellular defenses against IAV and MRSA infection, which occurs via the nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome. However, the activity and function of the NLRP3 inflammasome in MRSA pneumonia secondary to IAV infection remain unclear. To clarify this, we studied MRSA infection secondary to IAV both in vitro and in mouse model. The expression of the NLRP3 inflammasome was evaluated by quantitative reverse transcription polymerase chain reaction, immunofluorescence, Western blot, and enzyme-linked immunosorbent assay. The lung pathology and the rate of weight change were observed. We found that IAV infection for 1 week activated NLRP3 inflammasome. The enhanced expression of NLRP3, caspase-1, and cleaved caspase-1 was associated with MRSA infection secondary to IAV, but the expression of interleukin (IL)-1β decreased in superinfection with MRSA both in vitro and in vivo. The aggravated inflammatory pathology in MRSA pneumonia secondary to IAV infection was associated with decreased expression of IL-1β. And increased weight loss in MRSA pneumonia secondary to IAV infection was related to decreased concentration of IL-1β in serum. It infers that superinfection with MRSA reduces expression of IL-1β someway, and decreased expression of IL-1β impairs the host immunity and leads to aggravated pneumonia. These results contributed to our understanding of the detailed activity of the NLRP3 inflammasome, IL-1β, and their relationship with aggravation of MRSA pneumonia secondary to IAV infection. Immunotherapy targeting the IL-1β signaling pathway could be possible therapeutic strategy for secondary MRSA pneumonia.
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Project description:Effective clearance of neurotoxic amyloid-beta (Aβ) from the brain is a critical process to prevent Alzheimer's disease (AD). One major clearance mechanism is Aβ transcytosis mediated by low-density lipoprotein receptor-related protein 1 (LRP1) in capillary endothelial cells. A marked loss of endothelial LRP1 is found in AD brains and is believed to significantly impair Aβ clearance. Recently, we demonstrated that pro-inflammatory cytokines IL-1β, IL-6 and TNF-α, significantly down-regulated LRP1 in human primary microvascular endothelial cells (MVECs). In this study, we sought to determine the underlying molecular mechanism by which IL-1β led to LRP1 loss in MVECs. Reduced LRP1 protein and transcript were detected up to 24 h post-exposure and returned to the baseline levels after 48 h post-exposure with 1 ng/ml IL-1β. This reduction was in part mediated by microRNA-205-5p, -200b-3p, and -200c-3p, as these microRNAs were concomitantly upregulated in MVECs exposed to IL-1β. Synthetic microRNA-205-5p, -200b-3p, and -200c-3p mimics recapitulated LRP1 loss in MVECs without IL-1β, and their synthetic antagomirs effectively reversed IL-1β-mediated LRP1 loss. Importantly, we found that the expression of these three microRNAs was controlled by NF-κB as pharmacological NF-κB inhibitor, BMS-345541, inhibited the IL-1β-mediated upregulation of these microRNAs and rescued LRP1 expression. siRNA-mediated silencing of IκB in MVECs elevated microRNA-200b-3p and decreased LRP1 transcript, partially confirming our overall findings. In conclusion, our study provides a mechanism by which pro-inflammatory IL-1β instigates the suppression of LRP1 expression in MVECs. Our findings could implicate spatiotemporal loss of LRP1 and impairment of the LRP1-mediated clearance mechanism by endothelial cells.
| S-EPMC7796931 | biostudies-literature
Project description:Neuro-immune interaction during development is strongly implicated in the pathogenesis of neurodevelopmental disorders, but the mechanisms that cause neuronal circuit dysregulation are not well understood. We performed in vivo imaging of the developing retinotectal system in the larval zebrafish to characterize the effects of immune system activation on refinement of an archetypal sensory processing circuit. Acute inflammatory insult induced hyper-dynamic remodeling of developing retinal axons in larval fish and increased axon arbor elaboration over days. Using calcium imaging in GCaMP6s transgenic fish we showed that these morphological changes were accompanied by a shift toward decreased visual acuity in tectal cells. This finding was supported by poorer performance in a visually guided behavioral task. We further found that the pro-inflammatory cytokine, interleukin-1β (IL-1β) is upregulated by the inflammatory insult, and that down-regulation of IL-1β abrogated the effects of inflammation on axonal dynamics and growth. Moreover, baseline branching of the RGC arbors in IL-1β morphant animals was significantly different from that in control larvae, and their performance in a predation assay was impaired, indicating a role for this cytokine in normal neuronal development. This work establishes a simple and powerful non-mammalian model of developmental immune activation and demonstrates a role for IL-1β in mediating the pathological effects of inflammation on neuronal circuit development.SIGNIFICANCE STATEMENTMaternal immune activation (MIA) can increase the risk of neurodevelopmental disorders in offspring, however the mechanisms involved are not fully understood. Using a non-mammalian vertebrate model of developmental immune activation, we show that even brief activation of inflammatory pathways has immediate and long-term effects on the arborization of axons, and that these morphological changes have functional and behavioral consequences. Finally, we show that the pro-inflammatory cytokine IL-1β plays an essential role in both the effects of inflammation on circuit formation and normal axonal development. Our data add to a growing body of evidence supporting epidemiological studies linking immune activation to neurodevelopmental disorders, and help shed light on the molecular and cellular processes that contribute to the etiology of these disorders.
| S-EPMC8287996 | biostudies-literature
Project description:Diabetes mellitus (DM) encompasses a multitude of secondary disorders, including heart disease. One of the most frequent and potentially life threatening disorders of DM-induced heart disease is ventricular tachycardia (VT). Here we show that toll-like receptor 2 (TLR2) and NLRP3 inflammasome activation in cardiac macrophages mediate the production of IL-1β in DM mice. IL-1β causes prolongation of the action potential duration, induces a decrease in potassium current and an increase in calcium sparks in cardiomyocytes, which are changes that underlie arrhythmia propensity. IL-1β-induced spontaneous contractile events are associated with CaMKII oxidation and phosphorylation. We further show that DM-induced arrhythmias can be successfully treated by inhibiting the IL-1β axis with either IL-1 receptor antagonist or by inhibiting the NLRP3 inflammasome. Our results establish IL-1β as an inflammatory connection between metabolic dysfunction and arrhythmias in DM.
| S-EPMC5123037 | biostudies-literature
Project description:Th17 cells play a critical role in the adaptive immune response against extracellular bacteria, and the possible mechanisms by which they can protect against infection are of particular interest. In this study, we describe, to our knowledge, a novel IL-1β dependent pathway for secretion of the antimicrobial peptide IL-26 from human Th17 cells that is independent of and more rapid than classical TCR activation. We find that IL-26 is secreted 3 hours after treating PBMCs with Mycobacterium leprae as compared with 48 hours for IFN-γ and IL-17A. IL-1β was required for microbial ligand induction of IL-26 and was sufficient to stimulate IL-26 release from Th17 cells. Only IL-1RI+ Th17 cells responded to IL-1β, inducing an NF-κB-regulated transcriptome. Finally, supernatants from IL-1β-treated memory T cells killed Escherichia coli in an IL-26-dependent manner. These results identify a mechanism by which human IL-1RI+ "antimicrobial Th17 cells" can be rapidly activated by IL-1β as part of the innate immune response to produce IL-26 to kill extracellular bacteria.
| S-EPMC6684376 | biostudies-literature