Abstract:
:Alcohol-induced neuroinflammation is mediated by proinflammatory cytokines, including IL-1β. IL-1β production requires caspase-1 activation by inflammasomes-multiprotein complexes that are assembled in response to danger signals. We hypothesized that alcohol-induced inflammasome activation contributes to increased IL-1β in the brain. WT and TLR4-, NLRP3-, and ASC-deficient (KO) mice received an ethanol-containing or isocaloric control diet for 5 weeks, and some received the rIL-1ra, anakinra, or saline treatment. Inflammasome activation, proinflammatory cytokines, endotoxin, and HMGB1 were measured in the cerebellum. Expression of inflammasome components (NLRP1, NLRP3, ASC) and proinflammatory cytokines (TNF-α, MCP-1) was increased in brains of alcohol-fed compared with control mice. Increased caspase-1 activity and IL-1β protein in ethanol-fed mice indicated inflammasome activation. TLR4 deficiency protected from TNF-α, MCP-1, and attenuated alcohol-induced IL-1β increases. The TLR4 ligand, LPS, was not increased in the cerebellum. However, we found up-regulation of acetylated and phosphorylated HMGB1 and increased expression of the HMGB1 receptors (TLR2, TLR4, TLR9, RAGE) in alcohol-fed mice. NLRP3- or ASC-deficient mice were protected from caspase-1 activation and alcohol-induced IL-1β increase in the brain. Furthermore, in vivo treatment with rIL-1ra prevented alcohol-induced inflammasome activation and IL-1β, TNF-α, and acetylated HMGB1 increases in the cerebellum. Conversely, intracranial IL-1β administration induced TNF-α and MCP-1 in the cerebellum. In conclusion, alcohol up-regulates and activates the NLRP3/ASC inflammasome, leading to caspase-1 activation and IL-1β increase in the cerebellum. IL-1β amplifies neuroinflammation, and disruption of IL-1/IL-1R signaling prevents alcohol-induced inflammasome activation and neuroinflammation. Increased levels of acetylated and phosphorylated HMGB1 may contribute to alcoholic neuroinflammation.
journal_name
J Leukoc Bioljournal_title
Journal of leukocyte biologyauthors
Lippai D,Bala S,Petrasek J,Csak T,Levin I,Kurt-Jones EA,Szabo Gdoi
10.1189/jlb.1212659subject
Has Abstractpub_date
2013-07-01 00:00:00pages
171-82issue
1eissn
0741-5400issn
1938-3673pii
jlb.1212659journal_volume
94pub_type
杂志文章abstract::In an analysis of nitric oxide (.NO) production and toxicity, chicken macrophage-generated .NO inhibited mitochondrial activity in both .NO-producing macrophages themselves and lymphoid tumor targets. However, differences in targeting of mitochondrial toxicity were observed among these cells. Two chicken macrophage ce...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/jlb.56.1.52
更新日期:1994-07-01 00:00:00
abstract::The immunosuppressive activity of interleukin-10 (IL-10) makes this cytokine a potentially important clinical tool to reduce inflammatory responses in various diseases. Its efficacy as a therapeutic modality is dependent on the responsiveness of immune cells. We report that macrophages from mice chronically infected w...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:
更新日期:2001-10-01 00:00:00
abstract::The oxidative metabolic burst of stimulated human polymorphonuclear leukocytes (PMNs) has been evaluated by the measurement of oxygen consumption, chemiluminescence, and oxygen radicals (O2-, H2O2, OH-) derived from activation of the hexose monophosphate shunt (HMPS). PMNs from patients with chronic granulomatous dise...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/jlb.43.4.317
更新日期:1988-04-01 00:00:00
abstract::Histone acetylation has an important role in gene regulation, DNA replication, and repair. Because these processes are central to the development of the immune system, we investigated the role of a previously unstudied histone acetyltransferase named KAT7 (also known as Myst2 or HBO1) in the regulation of thymopoiesis...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.1MA0816-338R
更新日期:2017-04-01 00:00:00
abstract::The lectin jacalin interacts with the CD4 cell surface antigen; this lectin inhibits in vitro infection by human immunodeficiency virus type 1 without preventing virus binding on the host cell. The infection process is known to involve cellular events triggered by the binding of the viral external glycoprotein gp120 t...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/jlb.56.4.521
更新日期:1994-10-01 00:00:00
abstract::We have demonstrated previously that binding of ephrin-A1 to EphA receptors on human CD4(+) and CD8(+) T cells stimulates migration. Two EphA receptors have been reported in T cells: EphA1 at the protein level and EphA4 at the mRNA level. In this study, we wanted to investigate the expression profile of these receptor...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.0709497
更新日期:2010-06-01 00:00:00
abstract::Although the immune system may provide early protection against cancer, tumors may exploit the healing arm of the immune system to enhance their growth and metastasis. For example, myeloid derived suppressor cells (MDSCs) are thought to promote tumor growth by several mechanisms, including the suppression of T cell ac...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.1012531
更新日期:2014-02-01 00:00:00
abstract::Immune-checkpoint blockade therapy with antibodies targeting CTLA-4 and PD-1 has revolutionized melanoma treatment by eliciting responses that can be remarkably durable and is now advancing to other malignancies. However, not all patients respond to immune-checkpoint inhibitors. Extensive preclinical evidence suggests...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章,评审
doi:10.1189/jlb.5RI0116-013RR
更新日期:2016-08-01 00:00:00
abstract::Treatment of mice with a monoclonal antibody (mAb) designated NIMP-R10, directed against the CD11b polypeptide of the CD18/CD11b heterodimeric type 3 complement receptor (CR3), exacerbates listeriosis by preventing myelomonocytic cells from focusing at sites of infected hepatocytes in the liver. Under these conditions...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/jlb.52.1.130
更新日期:1992-07-01 00:00:00
abstract::In this report, the construction of a functional, immunocompetent, full-thickness skin equivalent (SE) is described, consisting of an epidermal compartment containing keratinocytes, melanocytes, and human LCs derived from the MUTZ-3 cell line (MUTZ-LC) and a fibroblast-populated dermal compartment. The CD1a(+)Langerin...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.0610374
更新日期:2011-11-01 00:00:00
abstract::Asthma is a chronic inflammatory disease of the airways that afflicts over 30 million individuals in the United States and over 300 million individuals worldwide. The inflammatory response in the airways is often characterized by the analysis of sputum, which contains multiple types of cells including neutrophils, mac...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/JLB.5MA0720-770RR
更新日期:2020-11-01 00:00:00
abstract::Although IFN-alpha forms the foundation of therapy for chronic hepatitis C, only a minority of patients has a sustained response to IFN-alpha alone. The antiviral activities of IFN-alpha formed the rationale for its use in viral hepatitis. However, IFN-alpha and the other Type I IFNs are also pleiotropic immune regula...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章,多中心研究
doi:10.1189/jlb.1006622
更新日期:2007-03-01 00:00:00
abstract::We investigated the capacity of counterflow-isolated human monocytes to independently synthesize thromboxane B2 (TxB2) and prostaglandin E2 (PGE2) when stimulated with bacterial lipopolysaccharide (LPS). Independent metabolism was confirmed by establishing different specific activities (dpm/ng) of TxB2 and PGE2 releas...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/jlb.44.5.376
更新日期:1988-11-01 00:00:00
abstract::TLRs are a class of pattern recognition receptors (PRRs) that detect invading microbes by recognizing pathogen-associated molecular patterns (PAMPs). Upon PAMP engagement, TLRs activate a signaling cascade that leads to the production of inflammatory mediators. The localization of TLRs, either on the plasma membrane o...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章,评审
doi:10.1002/JLB.3MIR1218-483RR
更新日期:2019-07-01 00:00:00
abstract::In this study we describe the isolation and characterization of a new chicken (Gallus gallus) chemokine. This molecule belongs to the C or gamma-chemokine family and is related to the mouse and human lymphotactin (Lptn). Mouse and human Lptn are distinguished from alpha and beta chemokines by the absence of two cystei...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/jlb.65.1.87
更新日期:1999-01-01 00:00:00
abstract::In this study, we test the hypothesis that cAMP, acting as an extracellular mediator, affects the physiology and function of human myeloid cells. The cAMP is a second messenger recognized as a universal regulator of several cellular functions in different organisms. Many studies have shown that extracellular cAMP exer...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.3A0513-302RR
更新日期:2014-07-01 00:00:00
abstract::Transition metals, including zinc, are essential to all living organisms. They are also toxic in high amounts, and their intracellular concentration must be tightly regulated. In this edition of JLB, Stocks et al. report that the zinc transporter, ZnT1 (SLC30A1) is induced by TLR4 activation in Mϕs, in which it contri...
journal_title:Journal of leukocyte biology
pub_type: 社论
doi:10.1002/JLB.4CE0520-256R
更新日期:2021-02-01 00:00:00
abstract::Galectin-3 (gal-3), a beta-galactoside-binding animal lectin, plays a role in cell-cell and cell-extracellular matrix interactions. Extracellular gal-3 modulates cell migration and adhesion in several physiological and pathological processes. Gal-3 is highly expressed in activated macrophages. Schistosoma mansoni eggs...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.1206747
更新日期:2007-08-01 00:00:00
abstract::Concanavalin A (Con A)-induced hepatitis is a model for human T cell-mediated hepatitis. We evaluated the role of L-selectin and intercellular adhesion molecule-1 (ICAM-1) in this model by injecting Con A intravenously in mice lacking L-selectin (L-selectin-/-), ICAM-1 (ICAM-1-/-), or both (L-selectin/ICAM-1-/-). Bloo...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.0905527
更新日期:2006-04-01 00:00:00
abstract::CD163, a monocyte and macrophage-specific surface glycoprotein, which is increased by interleukin-10 and glucocorticoids, is a scavenger receptor for hemoglobin/haptoglobin complexes. We report a rapid and highly reproducible rise in soluble CD163 in the plasma of human volunteers given intravenous lipopolysaccharide ...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:
更新日期:2002-10-01 00:00:00
abstract::M-CSF is a pleiotropic cytokine involved in the survival, proliferation, and differentiation of cells of the monocyte/macrophage lineage. M-CSF is produced by numerous cells including CD3-activated T cells. M-CSF serum levels are increased during acute graft rejection. We tested the in vitro production of M-CSF, GM-CS...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:
更新日期:2002-02-01 00:00:00
abstract::Pulmonary alveolar macrophages (AMphis) are incompetent to phagocytose unopsonized Pseudomonas aeruginosa, but ingestion by other macrophage phenotypes (i.e., peritoneal macrophages) occurs efficiently. The purpose of this study was to explore factors that might control such phenotypic differences. Our laboratory has ...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:
更新日期:2001-01-01 00:00:00
abstract::Human immunodeficiency virus type-1 (HIV-1)-associated dementia (HAD) is a neurodegenerative disease characterized by HIV infection and replication in brain tissue. HIV-1-infected monocytes overexpress inflammatory molecules that facilitate their entry into the brain. Prostanoids are lipid mediators of inflammation th...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:
更新日期:2000-09-01 00:00:00
abstract::Resting microglia comprise up to 13% of the cells in human central nervous system (CNS) white matter. Their large number and dendritic morphology make them ideally suited to survey the CNS for noxious stimuli. Upon activation microglia gradually lose dendritic processes and transform into typical phagocytic macrophage...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/jlb.56.6.732
更新日期:1994-12-01 00:00:00
abstract::We have investigated the role of the purinergic P2X7 receptor in the formation of multinucleated giant cells in human monocyte/macrophage cultures stimulated with either concanavalin A or phytohemagglutinin. Macrophage fusion can be blocked by a P2X7-selective pharmacological antagonist or by a mAb directed against th...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章,评审
doi:10.1002/jlb.66.5.723
更新日期:1999-11-01 00:00:00
abstract::IL-10 is a key anti-inflammatory cytokine secreted by activated macrophages as a feedback control mechanism to prevent excessive inflammatory responses. Here, we define multiple intracellular trafficking pathways involved in the secretion of newly synthesized IL-10 from macrophages following TLR4 activation with LPS, ...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.0412191
更新日期:2012-12-01 00:00:00
abstract::Extravasation of leukocytes is a crucial process in the immunological defense. In response to a local concentration of chemokines, circulating leukocytes adhere to and migrate across the vascular endothelium toward the inflamed tissue. The small guanosinetriphosphatase Rap1 plays an important role in the regulation of...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.0506357
更新日期:2006-12-01 00:00:00
abstract::IL-18 has a potential to up-regulate the Th1 and Th2 immune responses. It is known that IL-18, in synergy with IL-12, augments the Th1 response to bacterial infections, but it also augments the Th2 response to allergic disorders in the absence of IL-12. Although the Th1 and Th2 immune responses cross-regulate each oth...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章,评审
doi:10.1189/jlb.1012502
更新日期:2013-05-01 00:00:00
abstract::The human lysozyme (LZM) gene is highly methylated in LZM-nonexpressor immature myeloid and in nonmyeloid cells and unmethylated only in LZM-expressing cells. Extended methylation analyses of the CpG-poor 5' flanking region and of the exon 4 CpG island (both containing Alu elements) of the LZM gene were now performed....
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.0106005
更新日期:2006-12-01 00:00:00
abstract::Colostrum plays an important role in protecting newborn infants against acute gastrointestinal and respiratory infections. IgA antibodies have been considered the major effector component; however, the role of their receptors on colostral phagocytes, especially neutrophils, has not been studied. Here, we demonstrate t...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:
更新日期:2001-02-01 00:00:00