scholarly journals Downregulation of hsa_circ_0002198 inhibits keloid fibroblast activities in vitro by reducing NLRP3 inflammasome activity

BIOCELL ◽  
2022 ◽  
Vol 46 (5) ◽  
pp. 1289-1297
Author(s):  
LEI FU ◽  
JINGWEN JIANG ◽  
XUEWU CHEN ◽  
FENGTING ZHU ◽  
HUI ZHANG
Keyword(s):  
Nlrp3 Inflammasome ◽  
Keloid Fibroblast ◽  
Inflammasome Activity

scholarly journals BTK operates a phospho-tyrosine switch to regulate NLRP3 inflammasome activity

2021 ◽  
Vol 218 (11) ◽  
Author(s):  
Zsófia Agnes Bittner ◽  
Xiao Liu ◽  
Maria Mateo Tortola ◽  
Ana Tapia-Abellán ◽  
Sangeetha Shankar ◽  
...  
Keyword(s):  
Posttranslational Modifications ◽  
Nlrp3 Inflammasome ◽  
Drug Target ◽  
Cellular Localization ◽  
Inflammasome Activation ◽  
Tyrosine Residues ◽  
Tyrosine Modification ◽  
Inflammasome Activity

Activity of the NLRP3 inflammasome, a critical mediator of inflammation, is controlled by accessory proteins, posttranslational modifications, cellular localization, and oligomerization. How these factors relate is unclear. We show that a well-established drug target, Bruton’s tyrosine kinase (BTK), affects several levels of NLRP3 regulation. BTK directly interacts with NLRP3 in immune cells and phosphorylates four conserved tyrosine residues upon inflammasome activation, in vitro and in vivo. Furthermore, BTK promotes NLRP3 relocalization, oligomerization, ASC polymerization, and full inflammasome assembly, probably by charge neutralization, upon modification of a polybasic linker known to direct NLRP3 Golgi association and inflammasome nucleation. As NLRP3 tyrosine modification by BTK also positively regulates IL-1β release, we propose BTK as a multifunctional positive regulator of NLRP3 regulation and BTK phosphorylation of NLRP3 as a novel and therapeutically tractable step in the control of inflammation.

Diterpenoids from Callicarpa rubella and their in vitro anti-NLRP3 inflammasome activity

Fitoterapia ◽  
2020 ◽  
Vol 147 ◽  
pp. 104774
Author(s):  
Qing Li ◽  
Xue-Wen Wu ◽  
Qi Wang ◽  
Tian-Tian Sun ◽  
Qiang-Qiang Shi ◽  
...  
Keyword(s):  
Nlrp3 Inflammasome ◽  
Inflammasome Activity

scholarly journals NLRP3 inflammasome activity is upregulated in an in-vitro model of COPD exacerbation

PLoS ONE ◽  
2019 ◽  
Vol 14 (5) ◽  
pp. e0214622 ◽  
Author(s):  
Noy Nachmias ◽  
Sheila Langier ◽  
Rafael Y. Brzezinski ◽  
Matan Siterman ◽  
Moshe Stark ◽  
...  
Keyword(s):  
Nlrp3 Inflammasome ◽  
In Vitro Model ◽  
Copd Exacerbation ◽  
Vitro Model ◽  
Inflammasome Activity

scholarly journals ROS-Mediated NLRP3 Inflammasome Activity Is Essential for Burn-Induced Acute Lung Injury

2015 ◽  
Vol 2015 ◽  
pp. 1-16 ◽  
Author(s):  
Shichao Han ◽  
Weixia Cai ◽  
Xuekang Yang ◽  
Yanhui Jia ◽  
Zhao Zheng ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Inflammatory Cytokines ◽  
Nlrp3 Inflammasome ◽  
Lavage Fluid ◽  
Sterile Inflammation ◽  
Ros Scavenger ◽  
Inflammasome Activity

The NLRP3 inflammasome is necessary for initiating acute sterile inflammation. However, its role in the pathogenesis of burn-induced acute lung injury (ALI) is unknown. This study aimed to determine the role of the NLRP3 inflammasome and the signaling pathways involved in burn-induced ALI. We observed that the rat lungs exhibited enhanced inflammasome activity after burn, as evidenced by increased levels of NLRP3 expression and Caspase-1 activity and augmented inflammatory cytokines. Inhibition of NLRP3 inflammasome by BAY11-7082 attenuated burn-induced ALI, as demonstrated by the concomitant remission of histopathologic changes and the reduction of myeloperoxidase(MPO) activity, inflammatory cytokines in rat lung tissue, and protein concentrations in the bronchoalveolar lavage fluid (BALF). In thein vitroexperiments, we used AMs (alveolar macrophages) challenged with burn serum to mimic the postburn microenvironment and noted that the serum significantly upregulated NLRP3 inflammasome signaling and reactive oxygen species (ROS) production. The use of ROS scavenger N-acetylcysteine (NAC) partially reversed NLRP3 inflammasome activity in cells exposed to burn serum. These results indicate that the NLRP3 inflammasome plays an essential role in burn-induced ALI and that burn-induced NLRP3 inflammasome activity is a partly ROS-dependent process. Targeting this axis may represent a promising therapeutic strategy for the treatment of burn-induced ALI.

Panax notoginseng saponins attenuate neuroinflammation through TXNIP-mediated NLRP3 inflammasome activation in aging rats

2020 ◽  
Vol 21 ◽  
Author(s):  
Zhiyong Zhou ◽  
Menghan He ◽  
Qingqing Zhao ◽  
Dongfan Wang ◽  
Changcheng Zhang ◽  
...  
Keyword(s):  
Nlrp3 Inflammasome ◽  
Panax Notoginseng ◽  
Control Group ◽  
Inflammasome Activation ◽  
Panax Notoginseng Saponins ◽  
Aging Rats ◽  
Nlrp3 Inflammasome Activation ◽  
Bv2 Microglia ◽  
Old Rats

Introduction:: Microglia-mediated inflammatory responses play a crucial role in aging-related neurodegenerative diseases. The TXNIP/NLRP3 pathway is a key pathway leading to microglial activation. Panax notoginseng saponins (PNS) have been widely used for the treatment of stroke in China. Objective:: This study evaluates the anti-neuroinflammatory effect of PNS and investigates the mechanism via TXNIPmediated NLRP3 inflammasome activation in aging rats. Materials and Methods:: Eighteen-month-old Sprague-Dawley rats were randomly divided into the aging control group and PNS treated groups (n=15 each group). For PNS-treated groups, rats were administrated food with PNS at the doses of 10 mg/kg and 30 mg/kg for consecutive 6 months until they were 24-month old. Rats from the aging control group were given the same food without PNS. Two-month-old rats were purchased and given the same food until 6-month old as the adult control group (n = 15). Then, the cortex and hippocampus were rapidly harvested and deposited. H&E staining was used to assess histo-morphological changes. Western blotting was carried out to detect the protein expression. Immunofluorescence was employed to measure the co-localization of NLRP3, TXNIP and Iba-1. In vitro model was established by LPS+ATP coincubation in the BV2 microglia cell line. Results:: Aging rats exhibited increased activation of microglia, accompanied by a high level of IL-1β expression. Meanwhile, aging rats showed enhanced protein expression of TXNIP and NLRP3 related molecules, which co-localized with microglia. PNS treatment effectively reduced the number of degenerated neurons and reversed the activation of the TXNIP/NLRP3 inflammatory pathway. In vitro results showed that PNS up to 100 μg / ml had no significant toxicity on BV2 microglia. Discussion:: PNS (25, 50 μg/ml) effectively reduced the inflammatory response induced by LPS and ATP co-stimulation, thus inhibiting the expression of TXNIP/NLRP3 pathway-related proteins. Conclusion:: PNS treatment improved aging-related neuronal damage through inhibiting TXNIP mediated NLRP3 inflammasome activation, which provided a potential target for the treatment of inflammatory-related neurodegenerative diseases.

scholarly journals The Role of Melatonin on NLRP3 Inflammasome Activation in Diseases

Antioxidants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1020
Author(s):  
Burak Ibrahim Arioz ◽  
Emre Tarakcioglu ◽  
Melis Olcum ◽  
Sermin Genc
Keyword(s):  
Nlrp3 Inflammasome ◽  
Intracellular Signaling ◽  
Metabolic Diseases ◽  
Metabolic Stress ◽  
Clinical Importance ◽  
Rapid Identification ◽  
In Vivo Studies ◽  
Inflammasome Activation

NLRP3 inflammasome is a part of the innate immune system and responsible for the rapid identification and eradication of pathogenic microbes, metabolic stress products, reactive oxygen species, and other exogenous agents. NLRP3 inflammasome is overactivated in several neurodegenerative, cardiac, pulmonary, and metabolic diseases. Therefore, suppression of inflammasome activation is of utmost clinical importance. Melatonin is a ubiquitous hormone mainly produced in the pineal gland with circadian rhythm regulatory, antioxidant, and immunomodulatory functions. Melatonin is a natural product and safer than most chemicals to use for medicinal purposes. Many in vitro and in vivo studies have proved that melatonin alleviates NLRP3 inflammasome activity via various intracellular signaling pathways. In this review, the effect of melatonin on the NLRP3 inflammasome in the context of diseases will be discussed.

scholarly journals Role of ASM/Cer/TXNIP signaling module in the NLRP3 inflammasome activation

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Jianjun Jiang ◽  
Yining Shi ◽  
Jiyu Cao ◽  
Youjin Lu ◽  
Gengyun Sun ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Nlrp3 Inflammasome ◽  
Mrna Level ◽  
Scavenger Receptor ◽  
Nuclear Factor Κb ◽  
Inflammasome Activation ◽  
Mrna Levels ◽  
Irreversible Inhibitor ◽  
Nlrp3 Inflammasome Activation

Abstract Background This study aimed to explore the effects of ceramide (Cer) on NLRP3 inflammasome activation and their underlying mechanisms. Methods Lipopolysaccharide (LPS)/adenosine triphosphate (ATP)-induced NLRP3 inflammasome activation in J774A.1 cells and THP-1 macrophages was used as an in vitro model of inflammation. Western blotting and real-time PCR (RT-PCR) were used to detect the protein and mRNA levels, respectively. IL-1β and IL-18 levels were measured by ELISA. ASM assay kit and immunofluorescence were used to detect ASM activity and Cer content. Results Imipramine, a well-known inhibitor of ASM, significantly inhibited LPS/ATP-induced activity of ASM and the consequent accumulation of Cer. Additionally, imipramine suppressed the LPS/ATP-induced expression of thioredoxin interacting protein (TXNIP), NLRP3, caspase-1, IL-1β, and IL-18 at the protein and mRNA level. Interestingly verapamil, a TXNIP inhibitor, suppressed LPS/ATP-induced activation of TXNIP/NLRP3 inflammasome but did not affect LPS/ATP-induced ASM activation and Cer formation. TXNIP siRNA and verapamil inhibited C2-Cer-induced upregulation of TXNIP and activation of the NLRP3 inflammasome. In addition, the pretreatment of cells with sulfo-N-succinimidyl oleate (SSO), an irreversible inhibitor of the scavenger receptor CD36, blocked Cer-induced upregulation of nuclear factor-κB (NF-κB) activity, TXNIP expression, and NLRP3 inflammasome activation. Inhibition of NF-κB activation by SN50 prevented Cer-induced upregulation of TXNIP and activation of the NLRP3 inflammasome but did not affect CD36 expression. Conclusion This study demonstrated that the ASM/Cer/TXNIP signaling pathway is involved in NLRP3 inflammasome activation. The results documented that the CD36-dependent NF-κB-TXNIP signaling pathway plays an essential role in the Cer-induced activation of NLRP3 inflammasomes in macrophages.

scholarly journals Silica nanoparticles induce NLRP3 inflammasome activation in human primary immune cells

2017 ◽  
Vol 23 (8) ◽  
pp. 697-708 ◽  
Author(s):  
Diana M Gómez ◽  
Silvio Urcuqui-Inchima ◽  
Juan C Hernandez
Keyword(s):  
Physicochemical Properties ◽  
Silica Nanoparticles ◽  
Inflammatory Cytokines ◽  
Nlrp3 Inflammasome ◽  
Deep Understanding ◽  
Inflammasome Activation ◽  
Dependent Manner ◽  
Dose Dependent ◽  
Pro Inflammatory Cytokines

In recent years, the potential use of silica nanoparticles (SiNPs) among different biomedical fields has grown. A deep understanding of the physicochemical properties of nanoparticles (NPs) and their regulation of specific biological responses is crucial for the successful application of NPs. Exposure to NP physicochemical properties (size, shape, porosity, etc.) could result in deleterious effects on cellular functions, including a pro-inflammatory response mediated via activation of the NLRP3 inflammasome. The aim of this study was to evaluate the potential in vitro immunomodulatory effect of 12-nm and 200-nm SiNPs on the expression of pro-inflammatory cytokines and NLRP3 inflammasome components in human primary neutrophils and PBMCs. This study demonstrates that regardless of the size of the nanoparticles, SiNPs induce the production of pro-inflammatory cytokines in a dose-dependent manner. Induced IL-1β production after exposure to SiNPs suggests the involvement of NLRP3 inflammasome components participation in this process. In conclusion, SiNPs induce the production of pro-inflammatory cytokines in a dose-dependent manner. Furthermore, our data suggest that the production and release of IL-1β possibly occurs through the formation of the NLRP3 inflammasome.

Drug-eluting microneedles for self-administered treatment of keloids

TECHNOLOGY ◽  
2014 ◽  
Vol 02 (02) ◽  
pp. 144-152 ◽  
Author(s):  
Peng Xue ◽  
David Chen Loong Yeo ◽  
Yon Jin Chuah ◽  
Hong Liang Tey ◽  
Yuejun Kang ◽  
...  
Keyword(s):  
Clinical Supervision ◽  
Fibrous Tissue ◽  
Polyethylene Glycol Diacrylate ◽  
Glycol Diacrylate ◽  
Keloid Fibroblast ◽  
Culture Models ◽  
Drug Eluting ◽  
Good Potential ◽  
Microneedle Patch

Keloid is a long-term dermatological scarring disease characterized by disfiguring lesions resulting from overgrowth of dense fibrous tissue. Current therapeutics are ineffective, require clinical supervision and can be costly. This study investigated the use of microneedle technology in the self-management of keloid lesions. Specifically, a microneedle patch comprising of polyethylene glycol diacrylate (PEGDA) and encapsulating 5-fluorouracil (5-FU) has been developed for transdermal delivery. The microneedle patches showed requisite mechanical strength (hardness 45 ± 11 MPa, elastic modulus 0.66 ± 0.16 GPa) and were able to puncture porcine epidermis. The choice of PEGDA substrate enabled conformability to non-planar anatomical regions (e.g. elbow), with about 50% of the loaded 5-FU released during the first 12 hours. Thereafter, the microneedle efficacy was evaluated on in vitro keloid fibroblast culture models, where 5-FU loaded microneedles effectively abolished keloid fibroblast proliferation activity. In summary, we have developed a microneedle device with a good potential as an effective, economical and self-applied therapy for keloid scars.

Sign in / Sign up

Export Citation Format

Share Document