Abstract:
:TLRs mediate host defense against microbial pathogens by eliciting production of inflammatory mediators and activating expression of MHC, adhesion, and costimulatory molecules. Endotoxin tolerance limits excessive TLR-driven inflammation during sepsis and reprograms macrophage responses to LPS, decreasing expression of proinflammatory cytokines without inhibiting anti-inflammatory and antimicrobial mediators. Molecular mechanisms of reprogramming of TLR4 signaling upon in vivo induction of endotoxin tolerance are incompletely understood. We used an in vivo model of endotoxin tolerance, whereby C57BL/6 mice were i.p.-inoculated with LPS or PBS, followed by in vitro challenge of peritoneal or splenic macrophages with LPS to examine activation of IRAK4 and expression of negative regulatory molecules. Administration of LPS in vivo-induced endotoxin tolerance in peritoneal and splenic macrophages, as evidenced by decreased degradation of IκBα, suppressed phosphorylation of p38 and reduced expression of TNF-α, IL-6, and KC mRNA upon in vitro LPS challenge. Macrophages from control and endotoxin-tolerant mice exhibited comparable TLR4 mRNA levels and similar expression of IL-1RA and IL-10 genes. Endotoxin tolerization in vivo blocked TLR4-driven IRAK4 phosphorylation and activation in macrophages, while increasing expression of IRAK-M, SHIP-1, A20 mRNA, and A20 protein. Thus, induction of endotoxin tolerance in vivo inhibits expression of proinflammatory mediators via impaired activation of IRAK4, p38, and NF-κB and increases expression of negative regulators of TLR4 pathways.
journal_name
J Leukoc Bioljournal_title
Journal of leukocyte biologyauthors
Xiong Y,Medvedev AEdoi
10.1189/jlb.0611273subject
Has Abstractpub_date
2011-12-01 00:00:00pages
1141-8issue
6eissn
0741-5400issn
1938-3673pii
jlb.0611273journal_volume
90pub_type
杂志文章abstract::To understand the modulation and the behavior of glycocalyx elements during adhesion, we explored one of its components, the CD43 molecule, on human monocytic THP-1 cells exposed to cytokine stimulation and its redistribution during heterotypic adhesion to opsonized erythrocytes. First we demonstrated by immunofluores...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/jlb.61.5.609
更新日期:1997-05-01 00:00:00
abstract::cDNA cloning revealed the presence of two related but distinct types of human interleukin-8 (IL-8) receptors, type I (type A) and type II (type B). By immunizing rabbits with glutathione-S-transferase fused with the NH2-terminal domain of each type of IL-8 receptor, we prepared polyclonal antibodies that specifically ...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/jlb.57.1.180
更新日期:1995-01-01 00:00:00
abstract::Mast cells are immune sentinels and a driving force in both normal and pathological contexts of inflammation, with a prominent role in allergic hypersensitivities. Crosslinking of FcεRI by allergen-bound IgE Abs leads to mast cell degranulation, resulting in an early-phase response and release of newly synthesized pro...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/JLB.3A0320-434R
更新日期:2020-05-01 00:00:00
abstract::In resident mouse peritoneal macrophages, group IVA cytosolic phospholipase A(2) (cPLA(2)alpha) mediates arachidonic acid (AA) release and eicosanoid production in response to diverse agonists such as A23187, phorbol myristate acetate, zymosan, and the enterotoxin, okadaic acid (OA). cPLA(2)alpha is regulated by phosp...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.0308197
更新日期:2008-09-01 00:00:00
abstract::Corynebacterium parvum-treated mice produce large amounts of circulating nitrogen oxides and develop a severe liver injury in response to lipopolysaccharide (LPS). Concurrent administration of NG-monomethyl-L-arginine not only suppresses nitric oxide synthesis in these animals but also profoundly increases the hepatic...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/jlb.52.4.390
更新日期:1992-10-01 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::Neuronal damage in HIV infection results mainly from chronic activation of brain tissue and involves inflammation, oxidative stress, and glutamate-related neurotoxicity. Glutamate toxicity acts via two distinct pathways: an excitotoxic one, in which glutamate receptors are hyperactivated, and an oxidative one, in whic...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章,评审
doi:10.1189/jlb.0306153
更新日期:2006-11-01 00:00:00
abstract::RA is a chronic autoimmune disease characterized by accumulation of inflammatory cells within synovial joints. RA is associated with a failure of apoptosis of infiltrating leukocytes, thought to be a result of overexpression of prosurvival Bcl-2 proteins. Overexpression of Bcl-2 in hematopoietic cells can result in sp...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.0412190
更新日期:2013-04-01 00:00:00
abstract::Polyamines naturally occur in all living beings and play an important role in the regulation of cell proliferation, differentiation, and functional stimulation of terminally differentiated cells. Our studies, using specific inhibitors of polyamine biosynthesis such as alpha-difluoromethylornithine and methylglyoxal-bi...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/jlb.52.6.585
更新日期:1992-12-01 00:00:00
abstract::The adhesion molecule CD44 consists of many isoforms of which particularly CD44v7 is of major importance in hematopoietic progenitor cell homing. An increase of progenitor cells in the periphery was observed after treating mice with a CD44v7-specific antibody, concomitant with a substantially augmented marrow-repopula...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:
更新日期:2001-03-01 00:00:00
abstract::The receptor for urokinase plasminogen activator (uPAR; CD87) is a 50- to 65-kDa glycosylphosphatidylinositol (GPI)-anchored glycoprotein expressed by leukocytes and tumor cells where it facilitates uPA-dependent, plasmin-mediated pericellular proteolysis during cellular invasion. Because uPAR is inducibly shed into c...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/jlb.64.2.203
更新日期:1998-08-01 00:00:00
abstract::Leukocytes are a central cellular element of innate-immune defense in mammals. In addition to the generation of toxic oxygen radicals and nitric oxide, leukocytes express and secrete a broad array of antimicrobial proteins and peptides. In the study, an antimicrobial polypeptide was isolated and purified from human pe...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.0505280
更新日期:2005-11-01 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::Chemokines regulate the migration and the maturation of dendritic cells (DC) licensed by microbial constituents. We have recently found that the function of DC, including their ability to activate naïve, allogeneic CD4+ T cells, requires the autocrine/paracrine release of the nuclear protein high mobility group box 1 ...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.0306171
更新日期:2007-01-01 00:00:00
abstract::We have identified three distinct cell phenotypes with respect to the conditions under which cells became susceptible to TNF-mediated lysis. These conditions include: 1) treatment with the protein synthesis inhibitor, cycloheximide; 2) contact with activated macrophages, and 3) infection with vaccinia virus. Whereas v...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/jlb.53.1.37
更新日期:1993-01-01 00:00:00
abstract::When mouse peritoneal cells in early phase-inflammatory exudates were cultured in vitro, the number of polymorphonuclear leukocytes (PMNs) rapidly decreased, whereas the number of macrophages gradually increased during culture. Macrophage growth was also induced by addition of effete PMNs or their debris to macrophage...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/jlb.39.5.489
更新日期:1986-05-01 00:00:00
abstract::This short review focuses on the role of central nervous system (CNS) perivascular macrophages as targets of productive infection of the CNS. Data discussed include the importance of these cells as early targets of infection and their productive infection with AIDS. Many of the immune molecules on perivascular macroph...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章,评审
doi:10.1189/jlb.0503207
更新日期:2003-11-01 00:00:00
abstract::Although mouse models of inflammatory skin diseases such as psoriasis and atopic dermatitis fail to completely phenocopy disease in humans, they provide invaluable tools to examine the molecular and cellular mechanisms responsible for the epidermal hyperplasia, inflammation, and excess angiogenesis observed in human d...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.0607347
更新日期:2008-07-01 00:00:00
abstract::Neutrophil apoptosis leads to macrophage ingestion of intact senescent neutrophils. This may represent a neutrophil removal mechanism that is important both in the control of inflammatory tissue injury and for the normal resolution processes of inflammation. Because apoptosis is likely to be a key control process in c...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:
更新日期:1993-10-01 00:00:00
abstract::The promoters of the IL-8, MCP-1, and RANTES genes contain binding sites for the redox-responsive transcription factors AP-1 and NF-kappaB, which have been shown to be important for their expression. In this overview, we present evidence from our laboratories that the stimulus-specific regulation of these chemokines b...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章,评审
doi:10.1002/jlb.65.3.291
更新日期:1999-03-01 00:00:00
abstract::We identified fresh human leukocytes as an abundant source of the candidate epithelial tumor suppressor gene, Ecrg4, an epigenetically regulated gene, which unlike other tumor suppressor genes, encodes an orphan-secreted, ligand-like protein. In human cell lines, Ecrg4 gene expression was low, Ecrg4 protein undetectab...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.1011503
更新日期:2012-05-01 00:00:00
abstract::We investigated the kinetics of macrophage subpopulations and the expression of monocyte chemoattractant protein 1 (MCP-1) in a rat model of bleomycin-induced lung injury. Rat macrophage subpopulations were examined by immunohistochemistry using various anti-rat macrophage monoclonal antibodies (mAbs) and their prolif...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/jlb.56.6.741
更新日期:1994-12-01 00:00:00
abstract::We have shown that losartan, a selective inhibitor of AT1 receptors for angiotensin II (AII), inhibits the binding of [3H]fMLP to neutrophil receptors (FPR). Here, we analyze, in Wistar rats, the effect of losartan on neutrophil recruitment in the lung triggered by fMLP. We found that i.v. infusion of losartan (0.4-20...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:
更新日期:2000-11-01 00:00:00
abstract::An increase in intracellular calcium concentration is one of the major initial steps in B cell activation following antigen receptor (BCR) ligation. We show herein that in C57BL/6 murine B lymphocytes and in model cell lines, BCR-mediated calcium ion (Ca(2+)) influx occurs via highly selective Ca(2+) release-activated...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.0308193
更新日期:2009-02-01 00:00:00
abstract::Previously, we described a novel glycosylphosphatidyl inositol (GPI)-anchored glycoprotein (designated GPI-80) on human neutrophils and monocytes that may regulate beta(2) integrin-dependent neutrophil adherence and migration. However, the mechanism regulating beta(2) integrin remains to be clarified. To study this, w...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:
更新日期:2002-02-01 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::Macrophages play an important role in effector mechanisms of various chronic inflammatory diseases. We studied the effect of gluten, the agent inducing celiac disease, and other food antigens on the activation of macrophages. Nitric oxide (NO) and cytokine production were followed as markers of activation, using cultu...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/jlb.67.3.312
更新日期:2000-03-01 00:00:00
abstract::We evaluated the concept that the vascular entrance of both bacterial and nonbacterial particulate material could lead to hepatic parenchymal cell injury, either due to postphagocytic Kupffer cell activity or the margination of activated leukocytes in the liver. Injection of denatured, collagen-coated particles as wel...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/jlb.43.3.193
更新日期:1988-03-01 00:00:00
abstract::The activation of collagenase released by polymorphonuclear leukocytes (PMNs) has been extensively studied in vitro, but the activation of the enzyme in vivo is not fully understood. For further evaluation of the relative role of oxidative and proteolytic mechanisms in the activation of collagenase, PMNs were stimulat...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/jlb.60.5.598
更新日期:1996-11-01 00:00:00
abstract::The expression of beta 2-integrins on gammadelta T cells in naïve mice or those with experimental autoimmune encephalomyelitis (EAE) remains poorly characterized. We compared beta 2-integrin expression and cytokine production between gammadelta and alphabeta T cells over the acute course of EAE. We observed that unlik...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.0407263
更新日期:2008-01-01 00:00:00