scholarly journals A Purified Biflavonoid Extract From Selaginella moellendorffii Alleviates Gout Arthritis via NLRP3/ASC/Caspase-1 Axis Suppression

2021 ◽  
Vol 12 ◽  
Author(s):  
Xueyan Zhang ◽  
Yingbo Liu ◽  
Guangrui Deng ◽  
Bisheng Huang ◽  
Guoyin Kai ◽  
...  
Keyword(s):  
Mouse Model ◽  
Nlrp3 Inflammasome ◽  
Enzyme Linked Immunosorbent Assay ◽  
Acute Gout ◽  
Paw Edema ◽  
Inflammation Model ◽  
Caspase 1 ◽  
Cellular Inflammation ◽  
Tnf Α ◽  
Selaginella Moellendorffii

Background: Activation of nucleotide oligomerization domain-like receptor protein 3 (NLRP3) inflammasome plays a crucial role in gout. Selaginella moellendorffii has been confirmed effective for the treatment of gout in hospital preparations. Flavonoids, such as amentoflavone (AM), are the main active components of this medicine.Purpose: We aimed to investigate the flavonoid extract (TF) and AM's effects on NLRP3 inflammasome in vitro and their preventive effects on gout in vivo.Methods: LC-MS method was employed to investigate the chemical profile of TF. The cellular inflammation model was established by lipopolysaccharide (LPS) or monosodium urate (MSU) stimulation. The cell membrane integrality and morphological characteristics were determined by using Lactate dehydrogenase (LDH) assay kits, propidium iodide (PI) stain, and scanning electron microscopy (SEM). The inflammatory cytokines and NLRP3 inflammasome activation were determined using enzyme-linked immunosorbent assay (ELISA), quantitative real-time polymerase chain reaction (RT-PCR), immunofluorescence staining, and western blotting. The acute gout mouse model was induced by MSU injection into footpads, and then the paw edema, inflammatory mediators, and histological examination (HE) were analyzed.Results: The main constituents in TF are AM and robustaflavone. In the cellular inflammation model, TF down-regulated the levels of nitric oxide (NO), TNF-α, and LDH, suppressed NLRP3 inflammasome-derived interleukin-1β (IL-1β) secretion, decreased caspase-1 activation, repressed mature IL-1β expression, inhibited ASC speck formation and NLRP3 protein expression. In an acute gout mouse model, oral administration of TF to mice effectively alleviated paw edema, reduced inflammatory features, and decreased the levels of IL-1β in mouse foot tissue. Similarly, the characteristic constituent AM was also able to down-regulated the levels of NO, TNF-α, and LDH, down-regulate the mRNA expression of IL-1β, TNF-α, caspase-1, and NLRP3. Besides, the foot thickness, lymphocyte infiltration, and IL-1β level were also prevented by AM.Conclusion: The results indicated that TF and its main constituent AM alleviate gout arthritis via NLRP3/ASC/Caspase-1 axis suppression.

scholarly journals Shiga Toxins Activate the NLRP3 Inflammasome Pathway To Promote Both Production of the Proinflammatory Cytokine Interleukin-1β and Apoptotic Cell Death

2015 ◽  
Vol 84 (1) ◽  
pp. 172-186 ◽  
Author(s):  
Moo-Seung Lee ◽  
Haenaem Kwon ◽  
Eun-Young Lee ◽  
Dong-Jae Kim ◽  
Jong-Hwan Park ◽  
...  
Keyword(s):  
Cell Death ◽  
Nlrp3 Inflammasome ◽  
Apoptotic Cell ◽  
Apoptotic Cell Death ◽  
Interleukin 1Β ◽  
Dependent Manner ◽  
Shiga Toxins ◽  
Caspase 1 ◽  
Immune Signaling Pathway ◽  
Tnf Α

Shiga toxin (Stx)-mediated immune responses, including the production of the proinflammatory cytokines tumor necrosis-α (TNF-α) and interleukin-1β (IL-1β), may exacerbate vascular damage and accelerate lethality. However, the immune signaling pathway activated in response to Stx is not well understood. Here, we demonstrate that enzymatically active Stx, which leads to ribotoxic stress, triggers NLRP3 inflammasome-dependent caspase-1 activation and IL-1β secretion in differentiated macrophage-like THP-1 (D-THP-1) cells. The treatment of cells with a chemical inhibitor of glycosphingolipid biosynthesis, which suppresses the expression of the Stx receptor globotriaosylceramide and subsequent endocytosis of the toxin, substantially blocked activation of the NLRP3 inflammasome and processing of caspase-1 and IL-1β. Processing and release of both caspase-1 and IL-1β were significantly reduced or abolished in Stx-intoxicated D-THP-1 cells in which the expression of NLRP3 or ASC was stably knocked down. Furthermore, Stx mediated the activation of caspases involved in apoptosis in an NLRP3- or ASC-dependent manner. In Stx-intoxicated cells, the NLRP3 inflammasome triggered the activation of caspase-8/3, leading to the initiation of apoptosis, in addition to caspase-1-dependent pyroptotic cell death. Taken together, these results suggest that Stxs trigger the NLRP3 inflammasome pathway to release proinflammatory IL-1β as well as to promote apoptotic cell death.

scholarly journals Myrtenal and β-caryophyllene oxide screened from Liquidambaris Fructus suppress NLRP3 inflammasome components in rheumatoid arthritis

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Wen-xuan Li ◽  
Ping Qian ◽  
Yi-tong Guo ◽  
Li Gu ◽  
Jessore Jurat ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Molecular Docking ◽  
Nlrp3 Inflammasome ◽  
Network Pharmacology ◽  
Caryophyllene Oxide ◽  
Active Ingredients ◽  
Caspase 1 ◽  
Tnf Α ◽  
Cartilage Erosion ◽  
And Cartilage

Abstract Background Liquidambaris Fructus (LF) is the infructescence of Liquidambar formosana. In Traditional Chinese Medicine, LF has been used to treat joint pain, a common symptom of arthritis and rheumatism; however, a lack of pharmacological evidence has limited its applications in modern clinics. Therefore, this study aims to explore the protective effect of LF on rheumatoid arthritis (RA) and to identify its active ingredients. Methods Rats with adjuvant-induced arthritis (AIA) were divided into 4 groups and administered petroleum ether extract of LF (PEL), ethyl acetate extract of LF (EEL), water extract of LF (WEL), or piroxicam (PIR) respectively for 3 weeks. Two additional groups were used as normal control (NC) and model control (MC) and administered distilled water as a placebo. The clinical scores for arthritis, bone surface, synovial inflammation and cartilage erosion were used to evaluate the therapeutic efficacy of each treatment. The serum IL-1β and TNF-α level and the expression of NLRP3, IL-1β and caspase-1 p20 in the synovial tissue of AIA rats were evaluated by ELISA and Western blot. The active ingredients of LF were investigated using network pharmacology and molecular docking methods, and their inhibition of NLRP3 inflammasome activation was verified in the human rheumatoid arthritis fibroblast-like synovial cells (RA-FLS) model. Results PEL could alleviate paw swelling, bone and joint destruction, synovial inflammation and cartilage erosion in the AIA rats, with significantly superior efficacy to that of EEL and WEL. PEL reduced IL-1β and TNF-α serum levels, and attenuated the upregulation of NLRP3, IL-1β and caspase-1 p20 expression in the synovial tissue of AIA rats. Network pharmacology and molecular docking results indicated that myrtenal and β-caryophyllene oxide were the main two active ingredients of PEL, and these two compounds showed significant inhibition on TNF-α, NLRP3, IL-1β and caspase-1 p20 expression in RA-FLS. Conclusions Myrtenal and β-caryophyllene oxide screened from PEL could suppress the activation of NLRP3 inflammasome, thereby alleviating RA symptoms.

scholarly journals N-Acetylcysteine (NAC) Inhibits Synthesis of IL-18 in Macrophage by Suppressing NLRP3 Expression to Reduce the Production of IFN-γ from NK Cells

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Xiaopeng Liu ◽  
Xufeng Lu ◽  
Zhixiong Hu
Keyword(s):  
Mouse Model ◽  
Nk Cells ◽  
Enzyme Linked Immunosorbent Assay ◽  
Chronic Obstructive ◽  
Related Protein ◽  
Obstructive Pulmonary Disease ◽  
Copd Patients ◽  
Tnf Α ◽  
Ifn Γ ◽  
Nlrp3 Expression

Background. N-Acetylcysteine (NAC) had exerted antioxidation and anti-inflammation effects on chronic obstructive pulmonary disease (COPD) patients. However, its effect in regulating interleukin- (IL-) 18 was not fully understood. This study was designed to evaluate the specific mechanism of NAC regulating IL-18. Materials and Methods. A total of 112 COPD patients and 103 health individuals were recruited in the study. Cytokine level in patients’ serum was measured by enzyme-linked immunosorbent assay (ELISA). A COPD mouse model was established by administration of lipopolysaccharide (LPS) and cigarette smoke. The expression of cytokines was measured by ELISA and flow cytometry. Inflammasome-related protein was measured by Western blot. Result. NAC could effectively improve the immune status of COPD patients as well as the COPD mouse model by downregulating proinflammation and inflammation cytokines including IL-1β, interferon- (IFN-) γ, tumor necrosis factor- (TNF-) α, and IL-18. It also had the capability to suppress synthesis of IL-18 in macrophage to inhibit the secretion of IFN-γ from natural killer (NK) cells through influencing the inflammasome-related protein in macrophages. Conclusion. NAC could effectively inhibit the production of IL-18 by suppressing NLRP3 expression in macrophages to reduce the production of IFN-γ in NK cells.

Rapid Release of Interleukin-1β from Human Platelets Is Independent of NLRP3 and Caspase

2021 ◽  
Author(s):  
Gabrielle J. Pennings ◽  
Caroline J. Reddel ◽  
Mathew Traini ◽  
Magdalena Lam ◽  
Maaike Kockx ◽  
...  
Keyword(s):  
Nlrp3 Inflammasome ◽  
Human Platelets ◽  
Interleukin 1Β ◽  
Enzyme Linked Immunosorbent Assay ◽  
Thrombin Receptor ◽  
Classical Pathway ◽  
Receptor Agonists ◽  
Caspase 1 ◽  
Rapid Release ◽  
Transmission Electron

Abstract Objective Platelets are critical in mediating both rapid responses to injury and the development and progression of coronary disease. Several studies have shown that, after prolonged exposure to agonists, they produce and release inflammatory mediators including interleukin-1β (IL-1β), via the classical pathway (NLRP3 inflammasome and caspase-1 cleavage to release active IL-1β) as described for leukocytes. This study aimed to determine whether there is rapid release of IL-1β in response to soluble platelet agonists and whether such rapid release is NLRP3- and caspase-1-dependent. Methods and Results Using flow cytometry to detect platelet activation (and release of α and dense granule contents) and the combination of Western blotting, enzyme-linked-immunosorbent assay, and immunogold labeling transmission electron and immunofluorescence microscopy, we identified that resting human platelets contain mature IL-1β. Platelets release IL-1β within minutes in response to adenosine diphosphate (ADP), collagen, and thrombin receptor agonists, but not in response to conventional NLRP3 inflammasome agonists—lipopolysaccharide and adenosine triphosphate. The rapid release of IL-1β in response to ADP and thrombin receptor agonists was independent of caspases (including caspase-1) and NLRP3. Immature and mature IL-1β were identified as low-abundance proteins on transmission electron microscopy of human platelets, and were localized to the platelet cytosol, open canalicular system, and the periphery of α granules. Conclusion Unlike monocytes and neutrophils, human platelets are capable of rapid agonist- and time-dependent release of IL-1β by a mechanism which is independent of caspase-1 and NLRP3.

scholarly journals Sialylated human milk oligosaccharides prevent intestinal inflammation by inhibiting toll like receptor 4/NLRP3 inflammasome pathway in necrotizing enterocolitis rats

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Wenting Zhang ◽  
Jingqiu He-Yang ◽  
Wenjuan Tu ◽  
Xiaoying Zhou
Keyword(s):  
Membrane Potential ◽  
Human Milk ◽  
Nlrp3 Inflammasome ◽  
Interleukin 6 ◽  
Mitochondrial Membrane ◽  
Toll Like Receptor ◽  
Human Milk Oligosaccharides ◽  
Toll Like Receptor 4 ◽  
Caspase 1 ◽  
Tnf Α

Abstract Background Necrotizing enterocolitis (NEC) remains a fatal gastrointestinal disorder in neonates and has very limited therapeutic options. Sialylated human milk oligosaccharides (SHMOs) improve pathological changes in experimental NEC models. The objectives of this study were to investigate the involvement of NLRP3 inflammasome in NEC pathology and to explore the effects of SHMOs on toll-like receptor 4 (TLR4)/nuclear factor κB (NF-κB)/NLRP3 inflammatory pathway in experimental NEC. Methods The intestinal-tissue segments were collected from NEC infants, NLRP3 and caspase-1 positive cell were examined by immunohistochemistry. Newborn rats were hand-fed with formula containing or non-containing SHMOs (1500 mg/L) and exposed to hypoxia/cold stress to induce experimental NEC. The NEC pathological scores were evaluated; ileum protein expression of membrane TLR4 (mTLR4), inhibitor κB-α (IκB-α), NF-κB p65 subunit and phospho-NF-κB p65, as well as NLRP3 and caspase-1 were analyzed; ileum concentrations of interleukin-1β, interleukin-6, tumor necrosis factor-α (TNF-α) were also measured. Human colon epithelial Caco-2 cells were pre-treated with or without SHMOs and stimulated with TLR4 activator, lipopolysaccharide. Cell viabilities, mitochondrial membrane potential and supernatant matrix metalloprotease 2 (MMP-2) activities were analyzed. Results Increased frequencies of NLRP3 and caspase-1 positive cells were found in the lamina propria of damaged intestinal area of NEC neonates. SHMOs supplementation reduced NEC incidence and pathological damage scores of rats challenged with hypoxia/cold stress. Accumulation of interleukin-1β, interleukin-6 and TNF-α in NEC group were attenuated in SHMOs + NEC group. Protein expression of mTLR4, NLRP3 and caspase-1 were elevated, cytoplasmic IκB-α were reduced, nuclear phospho-NF-κB p65 were increased in the ileum of NEC rats. SHMOs supplementation ameliorated the elevation of mTLR4, NLRP3 and caspase-1, restored IκB-α in the cytoplasmic fraction and reduced phospho-NF-κB p65 in the nuclear fraction in the ileum of NEC rats. SHMOs pre-treatment improved Caco-2 cell viability, mitigated loss of mitochondrial membrane potential and modulated MMP-2 activities in the presence of lipopolysaccharide in-vitro. Conclusions This study provided clinical evidence of involvement of NLRP3 inflammasome in NEC pathology, and demonstrated the protective actions of SHMOs might be owing to the suppression of TLR4/NF-κB/NLRP3-mediated inflammation in NEC.

scholarly journals Impact of Cethromycin (ABT-773) Therapy on Microbiological, Histologic, Immunologic, and Respiratory Indices in a Murine Model of Mycoplasma pneumoniae Lower Respiratory Infection

2004 ◽  
Vol 48 (8) ◽  
pp. 2897-2904 ◽  
Author(s):  
Ana María Ríos ◽  
Asunción Mejías ◽  
Susana Chávez-Bueno ◽  
Mónica Fonseca-Aten ◽  
Kathy Katz ◽  
...  
Keyword(s):  
Mouse Model ◽  
Mycoplasma Pneumoniae ◽  
Pulmonary Function Tests ◽  
Statistical Significance ◽  
Etiologic Agent ◽  
Whole Body ◽  
Enzyme Linked Immunosorbent Assay ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Ifn Γ

ABSTRACT Mycoplasma pneumoniae is a major etiologic agent of acute lower respiratory infections. We evaluated the antimicrobial and immunologic effects of cethromycin (ABT-773), a ketolide antibiotic, for the treatment of M. pneumoniae pneumonia in a mouse model. Eight-week-old BALB/c mice were inoculated intranasally once with 106 CFU of M. pneumoniae on day 0. Treatment was started 24 h after inoculation. Groups of mice were treated subcutaneously with cethromycin at 25 mg/kg of body weight or with placebo daily until sacrifice. Five to ten mice per group were evaluated at days 1, 4, 7, and 10 after inoculation. Outcome variables included bronchoalveolar lavage (BAL) for M. pneumoniae quantitative culture and cytokine and chemokine concentration determinations by enzyme-linked immunosorbent assay (tumor necrosis factor alpha [TNF-α], gamma interferon [IFN-γ], interleukin-1β [IL-1β], IL-2, IL-4, IL-12, granulocyte-macrophage colony-stimulating factor, IL-8, monocyte chemoattractant protein 1 [MCP-1], and macrophage inflammatory protein 1α [MIP-1α]), histopathologic score of the lungs (HPS), and pulmonary function tests (PFT) using whole-body, unrestrained plethysmography at the baseline and post-methacholine exposure as indicators of airway obstruction (AO) and airway hyperresponsiveness (AHR), respectively. The cethromycin-treated mice had a greater reduction in M. pneumoniae culture titers than placebo-treated mice, reaching statistical significance on days 7 and 10 (P < 0.05). HPS was significantly reduced in cethromycin-treated mice compared with placebo-treated mice on days 4, 7, and 10 (P < 0.05). Cytokine concentrations in BAL samples were reduced in mice that received cethromycin, and the differences were statistically significant for 7 of the 10 cytokines measured (TNF-α, IFN-γ, IL-1β, IL-8, IL-12, MCP-1, and MIP-1α) on day 4 (P < 0.05). PFT values were improved in the cethromycin-treated mice, with AO and AHR significantly reduced on day 4 (P < 0.05). In this mouse model, treatment with cethromycin significantly reduced M. pneumoniae culture titers in BAL samples, cytokine and chemokine concentrations in BAL samples, histologic inflammation in the lungs, and disease severity as defined by AO and AHR.

scholarly journals Effect of Hedyotis diffusa Willd extract on gouty arthritis in rats

2021 ◽  
Vol 20 (1) ◽  
pp. 129-134
Author(s):  
LanFang Wang ◽  
Fang OuYang ◽  
Yan Ma ◽  
Rui Sun ◽  
ShiWei Tan ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Nlrp3 Inflammasome ◽  
Gouty Arthritis ◽  
Lavage Fluid ◽  
Enzyme Linked Immunosorbent Assay ◽  
Walking Behavior ◽  
Tnf Α ◽  
Hedyotis Diffusa ◽  
Gait Score ◽  
Synovial Tissues

Purpose: To investigate the effect of Hedyotis diffusa Willd extract (HDWE) on gouty arthritis in rats.Method: Monosodium urate (MSU) crystal was injected into the ankle joint of rats to establish a rat model of gouty arthritis. HDWE (4.8, 9.6 and 19.2 g/kg) was administered to the rats treated with MSU crystals. The walking behavior of the rats was observed daily, and the gait score was calculated to evaluate the Oswestry disability index of rats. Levels of IL-1β and TNF-α in lavage fluid of articularcavities were measured using enzyme linked immunosorbent assay (ELISA) kits. The synovial tissues of joint of control, model and 19.2 g/kg HDWE group rats were obtained and NLRP3 inflammasome was analysed by Western blot.Results: The results showed that HDWE ameliorated the symptoms of gouty arthritis and gait score in rats significantly (p < 0.05). Further pharmacological experiments showed that all doses of HDWE decreased the levels of inflammatory cytokines IL-1β and TNF-α (p < 0.05), and inhibited NLRP3, caspase-1, ASC, IL-1β and IL-18 protein expressions of the lavage fluid of articular cavities in MSU crystal-treated rats (p < 0.01).Conclusion: The results indicate that HDWE exhibits a significant effect in ameliorating gouty arthritis via inhibition NLRP3  inflammasome, and thus is a potential new drug choice for the treatment of gouty arthritis. Keywords: Hedyotis diffusa, Caspase, Gouty arthritis, Inflammatory cytokines, NLRP3 inflammasom

scholarly journals Malyngamide F Possesses Anti-Inflammatory and Antinociceptive Activity in Rat Models of Inflammation

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Zhuocheng Li ◽  
Lei Zhang ◽  
Zhichao Zhao
Keyword(s):  
Enzyme Linked Immunosorbent Assay ◽  
Paw Edema ◽  
Ear Edema ◽  
Inflammatory Models ◽  
Tnf Α ◽  
Antinociceptive Effects ◽  
Cotton Pellet ◽  
Anti Inflammatory ◽  
Clinical Conditions ◽  
Oral Doses

Objective. Inflammation and pain are involved in the pathophysiology of various clinical conditions. This investigation aims to probe the analgesic and anti-inflammatory activity of Maltoamide F. Methods. The possible toxicity of Maltoamide F was evaluated by an acute toxicity test. To assess the anti-inflammatory and antinociceptive effects of Maltoamide F on rats, the models of carrageenan-caused paw edema, xylene-induced ear edema, arachidonic-acid- (AA-) induced ear edema, formalin-caused plantar edema, and cotton-pellet-induced granuloma were established. Levels of TNF-α, PGE-2, and IL-6 were detected by enzyme-linked immunosorbent assay (ELISA). Results. Maltoamide F was safe at oral doses of 1–10 mg/kg for rats. Maltoamide F (1 mg/kg, 5 mg/kg, and 10 mg/kg) notably reduced carrageenan-induced edema percentage of paws in rats and decreased levels of PGE-2, IL-6, and TNF-α in homogenates of foot tissues. Maltoamide F (1 mg/kg, 5 mg/kg, and 10 mg/kg) reduced levels of PGE-2, IL-6, and TNF-α in foot tissues of formalin-induced rats. Maltoamide F (1 mg/kg, 5 mg/kg, and 10 mg/kg) repressed AA-induced increase of ear thickness in rats and reduced levels of PGE-2, IL-6, and TNF-α in homogenates of ear tissues. Maltoamide F (1 mg/kg, 5 mg/kg, and 10 mg/kg) reduced xylene-induced weight of ear edema in rats and reduced levels of PGE-2, IL-6, and TNF-α in homogenates of ear tissues. Maltoamide F (1 mg/kg, 5 mg/kg, and 10 mg/kg) reduced levels of PGE-2, IL-6, and TNF-α in homogenates of cotton ball granuloma of cotton-pellet-induced rats. Conclusions. Maltoamide F possessed anti-inflammatory and analgesic activity in inflammatory models of rats.

scholarly journals Cold-Inducible RNA-Binding Protein (CIRP) Potentiates Uric Acid-Induced IL-1β Production

2021 ◽  
Author(s):  
Yuya Fujita ◽  
Toru Yago ◽  
Haruki Matsumoto ◽  
Tomoyuki Asano ◽  
Naoki Matsuoka ◽  
...  
Keyword(s):  
Uric Acid ◽  
Nlrp3 Inflammasome ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Human Neutrophils ◽  
Enzyme Linked Immunosorbent Assay ◽  
Inflammasome Activation ◽  
Dependent Manner ◽  
Caspase 1

Abstract Background Gout is an autoinflammatory disease driven by interleukin-1 (IL-1) induction in response to uric acid crystals. IL-1β production is dependent on inflammasome activation, which requires a priming signal, followed by an activating signal. The cold-inducible RNA-binding protein (CIRP) has been recently identified as a damage-associated molecular pattern (DAMP). In this study, we evaluated the roles of CIRP in monosodium urate (MSU)-mediated IL-1β secretion using human neutrophils. Methods Human neutrophils were stimulated by MSU in the presence or absence of CIRP priming to determine NLRP3 inflammasome activation and subsequent caspase-1 activation and IL-1β production. Cellular supernatants were analyzed by enzyme-linked immunosorbent assay (ELISA) to determine the presence of IL-1β or caspase-1 (p20). The cellular supernatants and lysates were also analyzed by immunoblotting using anti-cleaved IL-1β or anti-cleaved caspase-1 antibodies. Additionally, pro-IL-1β and NLRP3 transcript levels were analyzed by real-time reverse transcription-PCR (RT-PCR). Results Neither CIRP nor MSU stimulation alone induced sufficient IL-1β secretion from neutrophils. However, MSU stimulation induced IL-1β secretion from CIRP-primed neutrophils in a dose-dependent manner. This MSU-induced IL-1β secretion from CIRP-primed neutrophils was accompanied by the induction of cleaved IL-1β (p17). Furthermore, cleaved caspase-1 was induced in the cellular lysates of CIRP/MSU-treated neutrophils. Additionally, CIRP stimulation induced the expression of pro-IL-1β mRNA and protein in neutrophils. Conclusions Our data indicate that CIRP, an endogenous stress molecule, triggers uric acid-induced mature IL-1β induction as a priming stimulus for NLRP3 inflammasome in human neutrophils. We propose that CIRP acts as an important proinflammatory stimulant that primes and activates inflammasome and pro-IL-1β processing in response to uric acid in innate immune cells.

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