Abstract:
:Aberrant activation of the NOD-like receptor (NLR) family, pyrin domain-containing protein 3 (NLRP3) inflammasome, triggers a pathogenic inflammatory response in many inherited neurodegenerative disorders. Inflammation has recently been associated with valosin-containing protein (VCP)-associated diseases, caused by missense mutations in the VCP gene. This prompted us to investigate whether NLRP3 inflammasome plays a role in VCP-associated diseases, which classically affects the muscles, bones, and brain. In this report, we demonstrate (i) an elevated activation of the NLRP3 inflammasome in VCP myoblasts, derived from induced pluripotent stem cells (iPSCs) of VCP patients, which was significantly decreased following in vitro treatment with the MCC950, a potent and specific inhibitor of NLRP3 inflammasome; (ii) a significant increase in the expression of NLRP3, caspase 1, IL-1β, and IL-18 in the quadriceps muscles of VCPR155H/+ heterozygote mice, an experimental mouse model that has many clinical features of human VCP-associated myopathy; (iii) a significant increase of number of IL-1β(+)F4/80(+)Ly6C(+) inflammatory macrophages that infiltrate the muscles of VCPR155H/+ mice; (iv) NLRP3 inflammasome activation and accumulation IL-1β(+)F4/80(+)Ly6C(+) macrophages positively correlated with high expression of TDP-43 and p62/SQSTM1 markers of VCP pathology in damaged muscle; and (v) treatment of VCPR155H/+ mice with MCC950 inhibitor suppressed activation of NLRP3 inflammasome, reduced the F4/80(+)Ly6C(+)IL-1β(+) macrophage infiltrates in the muscle, and significantly ameliorated muscle strength. Together, these results suggest that (i) NLRP3 inflammasome and local IL-1β(+)F4/80(+)Ly6C(+) inflammatory macrophages contribute to pathogenesis of VCP-associated myopathy and (ii) identified MCC950 specific inhibitor of the NLRP3 inflammasome with promising therapeutic potential for the treatment of VCP-associated myopathy.
journal_name
Inflammationjournal_title
Inflammationauthors
Nalbandian A,Khan AA,Srivastava R,Llewellyn KJ,Tan B,Shukr N,Fazli Y,Kimonis VE,BenMohamed Ldoi
10.1007/s10753-016-0449-5subject
Has Abstractpub_date
2017-02-01 00:00:00pages
21-41issue
1eissn
0360-3997issn
1573-2576pii
10.1007/s10753-016-0449-5journal_volume
40pub_type
杂志文章相关文献
INFLAMMATION文献大全abstract::The present study was designed to address the relationship between iron homeostasis and bone metabolism. Cultured hFOB 1.19 osteoblasts were incubated with selected concentrations of hepcidin (50, 100, and 200 nmol/L) for 20 h, harvested for extraction of total RNA and proteins, and the expression of ferroportin 1 was...
journal_title:Inflammation
pub_type: 杂志文章
doi:10.1007/s10753-011-9411-8
更新日期:2012-06-01 00:00:00
abstract::We analyzed the influence of heparins (unfractionated heparin, UFH and low molecular weight heparin certoparin) on the generation of IL-1ra, IL-6, IL-10, and IL-12p40 and from leukocyte fractions in vitro. Polymorphonuclear neutrophil leukocytes (PMN) and peripheral blood mononuclear cells (PBMC) from 16 different hea...
journal_title:Inflammation
pub_type: 杂志文章
doi:10.1023/a:1012883916991
更新日期:2001-10-01 00:00:00
abstract::Cepharanthine (CEP), a biscoclaurine alkaloid isolated from Stephania cepharantha Hayata, has been reported to have potent anti-inflammatory properties. However, the anti-inflammatory effects of CEP on a mouse model of lipopolysaccharide (LPS)-induced mastitis and its underlying molecular mechanisms remain to be eluci...
journal_title:Inflammation
pub_type: 杂志文章
doi:10.1007/s10753-013-9744-6
更新日期:2014-04-01 00:00:00
abstract::An inflammatory cytokine, tumor necrosis factor (TNF)-alpha, has been implicated in the pathogenesis of inflammatory lung diseases such as interstitial pneumonia (IP). To clarify the role of the inflammatory cytokine in the pathogenesis of lung inflammation, we introduced a murine TNF-alpha gene into murine lungs by t...
journal_title:Inflammation
pub_type: 杂志文章
doi:10.1023/a:1006992408052
更新日期:2000-02-01 00:00:00
abstract::The etiology of the most autoimmune disorders is largely yet to be understood. However, major target antigens have been determined against some of clinically important molecules of human autoimmune diseases, such as insulin in type 1 diabetes mellitus (T1DM). T1DM is believed to be resulted from immune-mediated destru...
journal_title:Inflammation
pub_type: 杂志文章,评审
doi:10.1007/s10753-012-9555-1
更新日期:2013-04-01 00:00:00
abstract::Factors affecting the retinoic acid modulated expression of mucin mRNA in rat tracheal cultures were studied. Actinomycin D had no effect on mucin mRNA in cultures grown with retinoic acid (RA+). The usual precipitous drop in mucin mRNA in cultures lacking retinoic acid (RA-) was prevented by actinomycin D. Cyclohexim...
journal_title:Inflammation
pub_type: 杂志文章
doi:10.1007/BF01535255
更新日期:1994-12-01 00:00:00
abstract::The effects of an intravenous injection (i.v.) of Sephadex beads (20 mg kg(-1)) were examined on bronchial responsiveness to ACh (1-200 microg kg(-1) i.v.) as well as on cell accumulation in guinea-pig lung. Bronchial hyperreactivity to ACh, measured as increase in pulmonary insufflation pressure (PIP), was observed 3...
journal_title:Inflammation
pub_type: 杂志文章
doi:10.1023/a:1021913009742
更新日期:1999-10-01 00:00:00
abstract::Osteoarthritis (OA) is a degenerative joint disease frequently seen in the elderly population. Sinapic acid (SA), a commonly found phenolic acid, has been pharmacologically evaluated for its anti-inflammation effects in various studies. To explore its potential therapeutic role for OA, rat chondrocytes were treated wi...
journal_title:Inflammation
pub_type: 杂志文章
doi:10.1007/s10753-017-0712-4
更新日期:2018-03-01 00:00:00
abstract::Several experiments have detected that melatonin exerts a marked influence on the inflammatory process. In the present study we evaluated the effect of exogenous melatonin on the experimental granulomatous tissues in rat. Our data show that subcutaneous administration of different doses of melatonin given daily during...
journal_title:Inflammation
pub_type: 杂志文章
doi:10.1023/b:ifla.0000049043.89586.89
更新日期:2004-08-01 00:00:00
abstract::Age-related macular degeneration (AMD) is the predominant cause of irreversible blindness in the elderly population. Despite intensive basic and clinical research, its pathogenesis remains unclear. However, evidence suggests that immunological and inflammatory factors contribute to the pathogenesis of AMD. A newly ide...
journal_title:Inflammation
pub_type: 杂志文章
doi:10.1007/s10753-011-9379-4
更新日期:2012-04-01 00:00:00
abstract::Increased susceptibility of neonates to infection may be related to defects in newborn neutrophil (PMN) functional activities, including altered responses to complement fragments (Cf) and defective microbicidal activity. We therefore compared the kinetics of newborn and adult bovine PMN membrane shape change responses...
journal_title:Inflammation
pub_type: 杂志文章
doi:10.1007/BF00914305
更新日期:1989-12-01 00:00:00
abstract::Exposure to ultraviolet (UV) light impairs the function of inflammatory cells. Urocanic acid (UCA) in an stratum corneum has been suggested as a mediator in the immunosuppression of lymphoid cells detected after irradiation with UVB (UV wavelengths 280-320 nm). In this study, we examined the effects of the two UCA iso...
journal_title:Inflammation
pub_type: 杂志文章
doi:10.1007/BF01487038
更新日期:1996-10-01 00:00:00
abstract::Central nervous system tuberculosis (CNS-TB) is caused by infection with Mycobacterium tuberculosis (Mtb). The inflammatory response following CNS-TB involves the activation of resident microglia and the infiltration of macrophages. However, it has not been clarified whether microglia can be polarized into the classic...
journal_title:Inflammation
pub_type: 杂志文章
doi:10.1007/s10753-015-0136-y
更新日期:2015-08-01 00:00:00
abstract::We aim to determine the extent of the CD40-CD40L pathway involvement in activated platelet-induced changes in human umbilical endothelial cells (HUVECs). Activated platelets were co-incubated with HUVECs in the presence or absence of CD40LmAb. HUVECs were also directly stimulated with rhCD40L. HUVEC endothelial cycloo...
journal_title:Inflammation
pub_type: 杂志文章
doi:10.1007/s10753-011-9427-0
更新日期:2012-06-01 00:00:00
abstract::CD4+ T cell subset imbalance plays an important role in the development of diabetic complications. Neutrophils have recently been known as the regulator of CD4+ T cell differentiation. However, whether neutrophils affect CD4+ T cell population in diabetes is still elusive. In this study, we investigated the effect of ...
journal_title:Inflammation
pub_type: 杂志文章
doi:10.1007/s10753-018-0913-5
更新日期:2019-04-01 00:00:00
abstract::T cells adhere to human dermal fibroblasts (HDF). This cellular interaction leads to a pronounced secretion of the proinflammatory cytokines IL-6 and IL-8 via a juxtacrine stimulation induced by HDF-associated IL-1. Upon stimulation, fibroblasts express various surface proteins such as MCH-I molecules, which may inter...
journal_title:Inflammation
pub_type: 杂志文章
doi:10.1023/a:1027310218934
更新日期:1997-08-01 00:00:00
abstract::Enzyme-inducing drugs such as phenobarbital (PB) increase serum concentrations of an acute-phase protein, alpha 1-acid glycoprotein (AGP), in man, dogs, and rats via an unknown mechanism. We studied the effects of PB on components of an acute inflammatory reaction in rats in order to determine if PB acts only on this ...
journal_title:Inflammation
pub_type: 杂志文章
doi:10.1007/BF00923344
更新日期:1991-12-01 00:00:00
abstract::The synthetic compound 7-4-[Bis-(2-hydroxyethyl)-amino]-butoxy-5-hydroxy-8-methoxy-2-phenylchromen-4-one (V8) is a novel flavonoid-derived compound. In this study, we investigated the effects of V8 on Toll-like receptor 4 (TLR4)-mediated inflammatory reaction in human cervical cancer SiHa cells and lipopolysaccharide ...
journal_title:Inflammation
pub_type: 杂志文章
doi:10.1007/s10753-015-0236-8
更新日期:2016-02-01 00:00:00
abstract::The bacterial keratitis causes viability loss and apoptosis in the corneal epithelial cells (CECs). The cyanidin-3-O-glucoside (C3G) benefits visual system and also possess anti-bacterial and anti-inflammatory potentials. In the current study, the effects of C3G on human CECs (HCECs) against bacterial lipopolysacchari...
journal_title:Inflammation
pub_type: 杂志文章
doi:10.1007/s10753-020-01194-0
更新日期:2020-06-01 00:00:00
abstract::High-mobility group box 1 (HMGB1) plays a key role in the development of acute lung injury (ALI). Propofol, a general anesthetic with anti-inflammatory properties, has been suggested to be able to modulate lipopolysaccharide (LPS)-induced ALI. In this study, we investigated the effects of propofol on the expression of...
journal_title:Inflammation
pub_type: 杂志文章
doi:10.1007/s10753-016-0330-6
更新日期:2016-06-01 00:00:00
abstract::Alveolar macrophages (AMs) can initiate lung inflammation by producing pro-inflammatory cytokines and chemokines, but they participate actively in the prevention of inflammation during acute lung injury (ALI). Heme oxygenase-1 (HO-1) is mainly expressed in AMs and has anti-inflammatory properties in ALI, but the anti-...
journal_title:Inflammation
pub_type: 杂志文章
doi:10.1007/s10753-011-9415-4
更新日期:2012-06-01 00:00:00
abstract::In our study, we explored the bidirectional communication via soluble factors between bone cells and endotoxin-stimulated splenic lymphocytes in an in vitro coculture model that mimics the inflammatory environment. Both the ability of lymphocytes to affect differentiation and immune properties of bone cells, osteoblas...
journal_title:Inflammation
pub_type: 杂志文章
doi:10.1007/s10753-012-9477-y
更新日期:2012-10-01 00:00:00
abstract::Inflammatory bowel disease (IBD) has received much attention due to its increasing worldwide incidence and potential increased risk of colorectal cancer. The protective function of a Rho-associated protein kinase inhibitor (Y-27632) against 2,4,6-trinitrobenzene sulfonic acid (TNBS) induced mouse colitis has been prov...
journal_title:Inflammation
pub_type: 杂志文章
doi:10.1007/s10753-019-01171-2
更新日期:2020-06-01 00:00:00
abstract::Whether lipopolysaccharide (LPS) can promote vasa vasorum (VV) proliferation for atherosclerosis in vivo is unclear. Eighteen rabbits with atherosclerosis were randomly assigned into one of three groups of six. Group A received biweekly injections of 10 mL saline after 2 weeks of balloon injury. Groups B and C receive...
journal_title:Inflammation
pub_type: 杂志文章
doi:10.1007/s10753-012-9468-z
更新日期:2012-08-01 00:00:00
abstract::Valnemulin reportedly regulates inflammatory responses in addition to its in vitro antibacterial activity. In this study, we established a mouse model of lipopolysaccharide (LPS)-induced inflammatory lung injury and investigated the effect of valnemulin (100 mg/kg) on acute lung injury (ALI) 8 h after LPS challenge. W...
journal_title:Inflammation
pub_type: 杂志文章
doi:10.1007/s10753-010-9186-3
更新日期:2010-10-01 00:00:00
abstract::The aim of this study was to investigate the effect of high-intensity swimming exercise (HISE) on atopic dermatitis (AD). For the study, we established an AD model in BALB/c mice by repeated local exposure of house dust mite extract (Dermatophagoides farinae extract, DFE) and 1-chloro-2,4-dinitrobenzene (CDNB) to the ...
journal_title:Inflammation
pub_type: 杂志文章
doi:10.1007/s10753-014-9843-z
更新日期:2014-08-01 00:00:00
abstract::Salidroside (Sal), a phenylpropanoid glycoside isolated from a popular traditional Chinese medicinal plant Rhodiola rosea L., possesses multiple pharmacological actions. This aim of this study is to investigate the effects of Sal against isoproterenol (ISO)-induced myocardial ischemia. Fifty male Sprague-Dawley rats w...
journal_title:Inflammation
pub_type: 杂志文章
doi:10.1007/s10753-015-0134-0
更新日期:2015-08-01 00:00:00
abstract::The original version of this article contained mistakes, and the authors would like to correct them. ...
journal_title:Inflammation
pub_type: 杂志文章,已发布勘误
doi:10.1007/s10753-018-0770-2
更新日期:2018-06-01 00:00:00
abstract::Streptococcus suis serotype 2 (SS2) is an emerging zoonosis, and meningitis is the most frequent clinical manifestation, but mechanism of its virulent factor, enolase (Eno), is unknown in meningitis. In this study, Eno was inducibly expressed and added to an in vitro Transwell co-culture model of the blood-brain barri...
journal_title:Inflammation
pub_type: 杂志文章
doi:10.1007/s10753-015-0298-7
更新日期:2016-04-01 00:00:00
abstract::By the use of the nuclear microprobe technique, the concentrations of zinc in isolated erythrocytes, platelets, and granulocytes were measured in patients with rheumatoid arthritis, other inflammatory arthritides, and scleroderma. Markedly reduced cellular zinc values were found compared to those measured in healthy s...
journal_title:Inflammation
pub_type: 杂志文章
doi:10.1007/BF00917591
更新日期:1985-06-01 00:00:00