Abstract:
:The role of the transcription factor nuclear factor of activated T cells (NFAT) was initially identified in T and B cell gene expression, but its role in regulating gene expression in macrophages during sepsis is not known. Our data show that NFATc3 regulates expression of inducible nitric oxide synthase (iNOS) in macrophages stimulated with lipopolysaccharide. Selective inhibition of NFAT by cyclosporine A and a competitive peptide inhibitor 11R-VIVIT inhibited endotoxin-induced expression of iNOS and nitric oxide (NO) release. Macrophages from NFATc3 knockout (KO) mice show reduced iNOS expression and NO release and attenuated bactericidal activity. Gel shift and chromatin immunoprecipitation assays show that endotoxin challenge increases NFATc3 binding to the iNOS promoter, resulting in transcriptional activation of iNOS. The binding of NFATc3 to the iNOS promoter is abolished by NFAT inhibitors. NFATc3 KO mice subjected to sepsis show that NFATc3 is necessary for bacterial clearance in mouse lungs during sepsis. Our study demonstrates for the first time that NFATc3 is necessary for macrophage iNOS expression during sepsis, which is essential for containment of bacterial infections.
journal_name
J Innate Immunjournal_title
Journal of innate immunityauthors
Ranjan R,Deng J,Chung S,Lee YG,Park GY,Xiao L,Joo M,Christman JW,Karpurapu Mdoi
10.1159/000362647subject
Has Abstractpub_date
2014-01-01 00:00:00pages
754-64issue
6eissn
1662-811Xissn
1662-8128pii
000362647journal_volume
6pub_type
杂志文章abstract::The formation of neutrophil extracellular traps (NETs) is a host defence mechanism, known to facilitate the entrapment and growth inhibition of many bacterial pathogens. It has been implicated that the translocation of myeloperoxidase (MPO) from neutrophilic granules to the nucleus is crucial to this process. Under di...
journal_title:Journal of innate immunity
pub_type: 杂志文章
doi:10.1159/000480386
更新日期:2018-01-01 00:00:00
abstract::Human immunodeficiency virus-1 (HIV-1) infection and the acquired immune deficiency syndrome (AIDS) pandemic remain global threats in the absence of a protective or a therapeutic vaccine. HIV-1 replication is reportedly inhibited by some cellular factors, including APOBEC3G (A3G) and APOBEC3F (A3F), which are well kno...
journal_title:Journal of innate immunity
pub_type: 杂志文章
doi:10.1159/000339402
更新日期:2012-01-01 00:00:00
abstract::The Drosophila larval cellular immune response involves cells (haemocytes) that can be recruited from a haematopoietic organ known as the lymph gland, as well as a sessile population of cells found just underneath the larval cuticle arranged in a segmental pattern. Overexpression of the Drosophila c-src homologue Src6...
journal_title:Journal of innate immunity
pub_type: 杂志文章
doi:10.1159/000191216
更新日期:2009-01-01 00:00:00
abstract::Withdrawal of iron from serum (hypoferraemia) is a conserved innate immune antimicrobial strategy that can withhold this critical nutrient from invading pathogens, impairing their growth. Hepcidin (Hamp1) is the master regulator of iron and its expression is induced by inflammation. Mice lacking Hamp1 from birth rapid...
journal_title:Journal of innate immunity
pub_type: 杂志文章
doi:10.1159/000447713
更新日期:2016-01-01 00:00:00
abstract::Immunoglobulin A nephropathy (IgAN) is the most common form of glomerulonephritis throughout the world. A majority (approx. 60%) of patients with IgAN experience disease exacerbations associated with an acute respiratory or gastrointestinal illness that appears to represent a viral infection. However, the exact mechan...
journal_title:Journal of innate immunity
pub_type: 杂志文章
doi:10.1159/000345255
更新日期:2013-01-01 00:00:00
abstract::Eiger is the sole TNF family member found in Drosophila melanogaster. This signaling molecule is induced during infection and is required for an appropriate immune response to many microbes; however, little is known about where eiger is produced. Here, we show that eiger is made in the fly's fat body during a Salmonel...
journal_title:Journal of innate immunity
pub_type: 杂志文章
doi:10.1159/000315050
更新日期:2010-01-01 00:00:00
abstract::In in vitro experiments, Chlamydia pneumoniae has been shown to infect macrophages and to accelerate foam cell formation. It has been hypothesized that the C. pneumoniae infection affects foam cell formation by suppressing the expression of liver X receptors (LXR), but whether such an event occurs in human atheroscler...
journal_title:Journal of innate immunity
pub_type: 杂志文章
doi:10.1159/000327522
更新日期:2011-01-01 00:00:00
abstract::Neutrophils are the most abundant cell type involved in the innate immune response. They are rapidly recruited to sites of injury or infection where they engulf and kill invading microorganisms. Neutrophil apoptosis, the process of programmed cell death that prevents the release of neutrophil histotoxic contents, is t...
journal_title:Journal of innate immunity
pub_type: 杂志文章,评审
doi:10.1159/000284367
更新日期:2010-01-01 00:00:00
abstract::Listeria monocytogenes is a facultative intracellular pathogen which can infect Drosophila melanogaster. Upon infection, Drosophila mounts an immune response including antimicrobial peptide production and autophagy activation. A set of previously published results prompted us to study the role of the deubiquitinating ...
journal_title:Journal of innate immunity
pub_type: 杂志文章
doi:10.1159/000360293
更新日期:2014-01-01 00:00:00
abstract::Infections with highly pathogenic avian influenza viruses (HPAIV) in humans lead to systemic disease associated with cytokine storm and multiorgan failure. In this study we aimed to identify the role of monocytes for the host response to HPAIV infection. Using genome-wide microarray analysis, we surprisingly demonstra...
journal_title:Journal of innate immunity
pub_type: 杂志文章
doi:10.1159/000346706
更新日期:2013-01-01 00:00:00
abstract::Mucosal surfaces line our body cavities and provide the interaction surface between commensal and pathogenic microbiota and the host. The barrier function of the mucosal layer is largely maintained by gel-forming mucin proteins that are secreted by goblet cells. In addition, mucosal epithelial cells express cell-bound...
journal_title:Journal of innate immunity
pub_type: 杂志文章,评审
doi:10.1159/000453594
更新日期:2017-01-01 00:00:00
abstract::Histones are small basic proteins and highly conserved among eukaryotes. Their main function is binding, packaging and organizing of DNA in the nucleus, but extracellular histones are also potent antimicrobial proteins. Here we found that Streptococcus pyogenes - an important human pathogen - protects itself from hist...
journal_title:Journal of innate immunity
pub_type: 杂志文章
doi:10.1159/000448039
更新日期:2016-01-01 00:00:00
abstract::Neutrophil-derived antimicrobial peptides and proteins (AMPs) play an important role in the defense against microbes. Absence of defense is illustrated by neutropenic patients with frequent bacterial and fungal infections. However, the specificity of the antimicrobial effects has not been adequately described. We set ...
journal_title:Journal of innate immunity
pub_type: 杂志文章
doi:10.1159/000317665
更新日期:2010-01-01 00:00:00
abstract::The host innate immune response, including the production of type-I IFN, represents the primary line of defense against invading viral pathogens. Of the hundreds of IFN-stimulated genes (ISGs) discovered to date, ISG15 was one of the first identified and shown to encode a ubiquitin-like protein that functions, in part...
journal_title:Journal of innate immunity
pub_type: 杂志文章,评审
doi:10.1159/000226245
更新日期:2009-01-01 00:00:00
abstract::The complement-like protein thioester-containing protein 1 (TEP1) is the hallmark effector molecule against Plasmodium ookinetes in the malaria vector Anopheles gambiae. We have previously shown that the knockdown of the noncatalytic clip domain serine protease CLIPA2 increased TEP1-mediated killing rendering mosquito...
journal_title:Journal of innate immunity
pub_type: 杂志文章
doi:10.1159/000443883
更新日期:2016-01-01 00:00:00
abstract::Porphyromonas gingivalis produces proteases capable of degrading cytokines, host heme proteins and some antimicrobial peptides. In this study, we show that P. gingivalis culture supernatants fully or partially degrade human neutrophil peptide alpha-defensins and human beta-defensins after 30 min. This observation sugg...
journal_title:Journal of innate immunity
pub_type: 杂志文章
doi:10.1159/000181015
更新日期:2009-01-01 00:00:00
abstract::Early interactions between natural killer (NK) and dendritic cells (DC) shape the immune response at the frontier of innate and adaptive immunity. Activated NK cells participate in maturation or deletion of DCs that remain immature. We previously demonstrated that infection with a high virulence (HV) population of the...
journal_title:Journal of innate immunity
pub_type: 杂志文章
doi:10.1159/000350242
更新日期:2013-01-01 00:00:00
abstract::Hemolytic uremic syndrome (HUS), a vascular disease characterized by hemolytic anemia, thrombocytopenia, and acute renal failure, is caused by enterohemorrhagic Shiga toxin (Stx)-producing bacteria, which mainly affect children. Besides Stx, the inflammatory response mediated by neutrophils (PMN) is essential to HUS e...
journal_title:Journal of innate immunity
pub_type: 杂志文章
doi:10.1159/000445770
更新日期:2016-01-01 00:00:00
abstract::Killer immunoglobulin-like receptors (KIRs) recognize class I major histocompatibility complex molecules and participate in the calibration of activation thresholds during human natural killer (NK) cell development. The stochastic expression pattern of the KIR repertoire follows the product rule, meaning that the prob...
journal_title:Journal of innate immunity
pub_type: 杂志文章,评审
doi:10.1159/000323929
更新日期:2011-01-01 00:00:00
abstract:BACKGROUND:Pseudomonas aeruginosa (PS) infection results in severe morbidity and mortality, especially in immune-deficient populations. Aerobic exercise (AE) modulates the immune system, but its effects on the outcomes of pulmonary PS infection in elderly mice are unknown. METHODS:BALB/c mice (24 weeks old) were rando...
journal_title:Journal of innate immunity
pub_type: 杂志文章
doi:10.1159/000488953
更新日期:2018-01-01 00:00:00
abstract::Ficolins are a group of oligomeric lectins with subunits consisting of both collagen-like and fibrinogen-like domains. The majority of ficolins identified in vertebrates and invertebrates to date recognize N-acetylglucosamine (GlcNAc). X-ray crystallographic analysis of human ficolins has shown that the fibrinogen-lik...
journal_title:Journal of innate immunity
pub_type: 杂志文章,评审
doi:10.1159/000228160
更新日期:2010-01-01 00:00:00
abstract::Fibroblasts are known to eliminate intracellular bacteria, but the lethal hit of the bactericidal mechanism has not been defined. We show that primary embryonic and established fibroblasts can be induced by interferons or by intracellular bacterial infection to express a perforin-like mRNA previously described as macr...
journal_title:Journal of innate immunity
pub_type: 杂志文章
doi:10.1159/000345249
更新日期:2013-01-01 00:00:00
abstract::There is increasing evidence that the immune system is regulated by circadian rhythms. A wide range of immune parameters, such as the number of red blood cells and peripheral blood mononuclear cells as well as the level of critical immune mediators, such as cytokines, undergo daily fluctuations. Current experimental d...
journal_title:Journal of innate immunity
pub_type: 杂志文章,评审
doi:10.1159/000342427
更新日期:2013-01-01 00:00:00
abstract::Atherosclerosis is a chronic inflammatory disease characterized by dyslipidemia and accumulation of lipids in the arterial intima, with activation of both innate and adaptive immunity. Reciprocally, dyslipidemia associated with atherosclerosis can perturb normal immune function. Natural killer T (NKT) cells are a spec...
journal_title:Journal of innate immunity
pub_type: 杂志文章,评审
doi:10.1159/000296915
更新日期:2010-01-01 00:00:00
abstract::As a key molecule in the antiviral innate immune response, the activation of TANK-binding kinase 1 (TBK1) is under tight regulation. In this report, we identified phosphatidylserine-specific phospholipase PLA1A as a host factor that modulates the TBK1 activation. Knockdown of PLA1A expression suppressed the innate imm...
journal_title:Journal of innate immunity
pub_type: 杂志文章
doi:10.1159/000489832
更新日期:2018-01-01 00:00:00
abstract::The phagocyte NADPH oxidase, crucial for innate immunity, is dormant in resting cells, but becomes activated during phagocytosis to produce superoxide, a precursor of microbicidal oxidants. In activation of the oxidase, the multidomain protein p67(phox)plays a central role: it translocates to the membrane as a ternary...
journal_title:Journal of innate immunity
pub_type: 杂志文章
doi:10.1159/000235656
更新日期:2009-01-01 00:00:00
abstract:BACKGROUND:We have previously identified the upregulation of the innate immune response, neutrophil activation, and apoptosis during anaphylaxis using a microarray approach. This study aimed to validate the differential gene expression and investigate protein concentrations of "hub genes" and upstream regulators during...
journal_title:Journal of innate immunity
pub_type: 杂志文章
doi:10.1159/000492301
更新日期:2019-01-01 00:00:00
abstract::There is incomplete mechanistic understanding of the mobilization of neutrophils in the systemic and local compartment in smokers with chronic obstructive pulmonary disease (COPD). In this pilot study, we characterized how the adhesion molecules CD11b and CD62L, surface markers indicative of priming, are altered as ne...
journal_title:Journal of innate immunity
pub_type: 杂志文章
doi:10.1159/000509715
更新日期:2020-01-01 00:00:00
abstract::Monocytes (Mos) play an important role in the pathogenesis of intestinal mucosal inflammation. This study aims to investigate the mechanism by which the intestinal epithelial cell-derived thrombospondin 1 (TSP1) modulates Mo properties and regulates intestinal inflammatory responses. In this study, the production of T...
journal_title:Journal of innate immunity
pub_type: 杂志文章
doi:10.1159/000398799
更新日期:2015-01-01 00:00:00
abstract::Activation of complement leads to generation of the 3 anaphylatoxins C3a, C4a, and C5a. Although all 3 peptides are structurally similar, only C3a and C5a share a similar functional profile that includes the classic inflammatory activities and, more recently, developmental homing and regenerative properties among othe...
journal_title:Journal of innate immunity
pub_type: 杂志文章,评审
doi:10.1159/000371423
更新日期:2015-01-01 00:00:00