scholarly journals Sitafloxacin Inhibits TNFα Release from Monocytic THP-1 Cells Stimulated by LPS

2021 ◽  
Author(s):  
Ippei Sakamaki ◽  
Michika Fukushi ◽  
Kazuhiro Itoh ◽  
Wakana Ohashi ◽  
Kei Tomihara ◽  
...  
Keyword(s):  
Septic Shock ◽  
Inflammatory Cytokines ◽  
Anaerobic Bacteria ◽  
Systemic Reaction ◽  
Dependent Manner ◽  
Antimicrobial Spectrum ◽  
Gram Negative ◽  
Cytokines And Chemokines ◽  
Mechanism Of Inhibition ◽  
Dose Dependent

Abstract Sepsis is a systemic reaction to infection and excessive production of inflammatory cytokines and chemokines. It sometimes results in septic shock. The present study was designated to find out which quinolone antibiotic reduces TNFα production the most and to elucidate its mechanisms. We examined which quinolone antibiotic reduced TNFα production from THP-1 cells stimulated by lipopolysaccharide (LPS). Then, we examined the mechanism of inhibition of TNFα production by the antibiotic. STFX most effectively reduced TNFα concentrations within LPS-stimulated THP-1 cells supernatant. STFX suppressed TNFα production in a dose-dependent manner. We found that STFX did not inhibit the NF-kB, ERK, or p38 pathways, nor did it inhibit the production of TNFα mRNA. The percentage of intracellular TNFα was increased in cells stimulated by LPS and with STFX compared to that of cells stimulated by LPS alone. In conclusion, one of the mechanisms reducing TNFα production from LPS-stimulated THP-1 cells treated with STFX involves inhibition of TNFα release from these cells. STFX has a broad antimicrobial spectrum for gram-positive, gram-negative, and anaerobic bacteria, and may be effective for treating sepsis by both killing bacteria and suppressing inflammation.

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.

scholarly journals Dectin-1-Mediated Production of Pro-Inflammatory Cytokines Induced by Yeast β-Glucans in Bovine Monocytes

2021 ◽  
Vol 12 ◽  
Author(s):  
Ana R. V. Pedro ◽  
Tânia Lima ◽  
Ricardo Fróis-Martins ◽  
Bárbara Leal ◽  
Isabel C. Ramos ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Surface ◽  
Inflammatory Cytokines ◽  
Surface Expression ◽  
Cell Surface Receptor ◽  
Dependent Manner ◽  
Feed Supplements ◽  
Surface Receptor ◽  
Dose Dependent ◽  
Pro Inflammatory Cytokines

Yeast-derived products containing β-glucans have long been used as feed supplements in domesticated animals in an attempt to increase immunity. β-glucans are mainly recognized by the cell surface receptor CLEC7A, also designated Dectin-1. Although the immune mechanisms elicited through Dectin-1 activation have been studied in detail in mice and humans, they are poorly understood in other species. Here, we evaluated the response of bovine monocytes to soluble and particulate purified β-glucans, and also to Zymosan. Our results show that particulate, but not soluble β-glucans, can upregulate the surface expression of costimulatory molecules CD80 and CD86 on bovine monocytes. In addition, stimulated cells increased production of IL-8 and of TNF, IL1B, and IL6 mRNA expression, in a dose-dependent manner, which correlated positively with CLEC7A gene expression. Production of IL-8 and TNF expression decreased significantly after CLEC7A knockdown using two different pairs of siRNAs. Overall, we demonstrated here that bovine monocytes respond to particulate β-glucans, through Dectin-1, by increasing the expression of pro-inflammatory cytokines. Our data support further studies in cattle on the induction of trained immunity using dietary β-glucans.

scholarly journals UBQLN2 Promotes the Production of Type I Interferon via the TBK1-IRF3 Pathway

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1205
Author(s):  
Tianhong Chen ◽  
Wenjuan Zhang ◽  
Bo Huang ◽  
Xuan Chen ◽  
Cao Huang
Keyword(s):  
Inflammatory Cytokines ◽  
Type I Interferon ◽  
Complete Loss ◽  
Functional Assay ◽  
Type I ◽  
Dependent Manner ◽  
Frontotemporal Degeneration ◽  
Dose Dependent ◽  
Lateral Sclerosis ◽  
Pro Inflammatory Cytokines

Mutations of Ubiquilin 2 (UBQLN2) or TANK-binding kinase 1 (TBK1) are associated with amyotrophic lateral sclerosis and frontotemporal degeneration (ALS/FTD). However, the mechanisms whereby UBQLN2 or TBK1 mutations lead to ALS and FTD remain unclear. Here, we explored the effect of UBQLN2 on TBK1 in HEK-293T cells or in CRISPR–Cas9-mediated IRF3 and IRF7 knockout (KO) cells. We found an interaction between TBK1 and UBQLN2, which was affected by ALS/FTD-linked mutations in TBK1 or UBQLN2. Co-expression of UBQLN2 with TBK1 elevated the protein level of TBK1 as well as the phosphorylation of TBK1 and IRF3 in a UBQLN2 dose-dependent manner, and this phosphorylation was reduced by mutant UBQLN2. In addition, the cellular production of IFN1 and related pro-inflammatory cytokines was substantially elevated when UBQLN2 and TBK1 were co-expressed, which was also decreased by mutant UBQLN2. Functional assay revealed that mutant UBQLN2 significantly reduced the binding affinity of TBK1 for its partners, including IRF3, (SQSTM1)/p62 and optineurin (OPTN). Moreover, complete loss of IRF3 abolished the induction of IFN1 and related pro-inflammatory cytokines enhanced by UBQLN2 in HEK-293T cells, whereas no significant change in IRF7 knockout cells was observed. Thus, our findings suggest that UBQLN2 promotes IRF3 phosphorylation via TBK1, leading to enhanced IFN1 induction, and also imply that the dysregulated TBK1-IRF3 pathway may play a role in UBQLN2-related neurodegeneration.

PHOSPHOLIPID RICH EMULSION IMPROVED SURVIVAL AND CARDIOVASCULAR STATUS IN PORCINE SEPTIC SHOCK IN A DOSE-DEPENDENT MANNER

1999 ◽  
Vol 27 (Supplement) ◽  
pp. A158 ◽  
Author(s):  
Roy D Goldfarb ◽  
Thomas S Parker ◽  
Daniel M Levine ◽  
Bruce R Gordon ◽  
Albert L Rubin ◽  
...  
Keyword(s):  
Septic Shock ◽  
Dependent Manner ◽  
Dose Dependent

scholarly journals SARS-CoV-2 spike protein induces inflammation via TLR2-dependent activation of the NF-κB pathway

2021 ◽  
Author(s):  
Shahanshah Khan ◽  
Mahnoush S. Shafiei ◽  
Christopher Longoria ◽  
John Schoggins ◽  
Rashmin C. Savani ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Inflammatory Response ◽  
Inflammatory Cytokines ◽  
Lung Epithelial Cells ◽  
Dependent Manner ◽  
S Protein ◽  
Cytokines And Chemokines ◽  
Lung Epithelial ◽  
Mouse Macrophages ◽  
Human And Mouse

Pathogenesis of COVID-19 is associated with a hyperinflammatory response; however, the precise mechanism of SARS-CoV-2-induced inflammation is poorly understood. Here we investigated direct inflammatory functions of major structural proteins of SARS-CoV-2. We observed that spike (S) protein potently induces inflammatory cytokines and chemokines including IL-6, IL-1b, TNFa, CXCL1, CXCL2, and CCL2, but not IFNs in human and mouse macrophages. No such inflammatory response was observed in response to membrane (M), envelope (E), and neucleocapsid (N) proteins. When stimulated with extracellular S protein, human lung epithelial cells A549 also produce inflammatory cytokines and chemokines. Interestingly, epithelial cells expressing S protein intracellularly are non-inflammatory, but elicit an inflammatory response in macrophages when co-cultured. Biochemical studies revealed that S protein triggers inflammation via activation of the NF-kB pathway in a MyD88-dependent manner. Further, such an activation of the NF-kB pathway is abrogated in Tlr2-deficient macrophages. Consistently, administration of S protein induces IL-6, TNF-a, and IL-1b in wild-type, but not Tlr2-deficient mice. Together these data reveal a mechanism for the cytokine storm during SARS-CoV-2 infection and suggest that TLR2 could be a potential therapeutic target for COVID-19.

scholarly journals Herbal Medication, Macmoondong Decoction, Attenuates LPS-Induced COPD in Small Airways via TGF-β, CCL-2, and CXCL1

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Soon-Young Lee ◽  
Bossng Kang ◽  
Chun-Sik Bae ◽  
Seung-Sik Cho ◽  
Dae-Hun Park
Keyword(s):  
Morphological Changes ◽  
World Health ◽  
Chronic Obstructive ◽  
Small Airways ◽  
Dependent Manner ◽  
Obstructive Pulmonary Disease ◽  
Cytokines And Chemokines ◽  
Incurable Disease ◽  
Health Organization ◽  
Dose Dependent

Chronic obstructive pulmonary disease (COPD) is an incurable disease related to the respiratory system. A 2017 report by the World Health Organization stated that it was the third most common cause of death in 2015. Macmoondong decoction is a prescription that has been used widely in Korea for the treatment of respiratory diseases, but there have been few investigations into the therapeutic mechanism. To investigate the anti-COPD effect of macmoondong decoction, the animals were divided into five treatment groups: control; COPD-induced control; Spiriva; 150 mg/kg macmoondong decoction; and 1500 mg/kg macmoondong decoction. Changes typically observed in COPD, such as the populations of WBC and neutrophils in BALF, the level of IgE in serum, morphological changes, the DNA levels, and the protein expression of cytokines and chemokines (TGF-β, CCL-2, CXCL1, and CXCL11) in the pulmonary system, were evaluated. Macmoondong decoction inhibited the populations of WBC and neutrophils in BALF and the level of IgE in serum. Dose-dependent prevention of the pulmonary morphological changes, such as emphysema and airway fibrosis, was observed. Macmoondong decoction suppressed the expression of DNA and proteins related to the occurrence of COPD, such as TGF-β, CCL-2, CXCL1, and CXCL11. In particular, the expression of TGF-β, CCL-2, and CXCL1 was significantly suppressed by 1500 mg/kg macmoondong decoction treatment compared with Spiriva treatment. Macmoondong decoction exerted an anti-COPD effect, and the mechanism of its action may be the suppression of TGF-β, CCL-2, CXCL1, and CXCL11 expression, which occurred in a dose-dependent manner. The mechanism of action of macmoondong decoction may be the dose-dependent suppression of TGF-β, CCL-2, CXCL1, and CXCL11, with TGF-β, CCL-2, and CXCL1 as the potential key factors involved in COPD suppression.

scholarly journals New Thiazole Nortopsentin Analogues Inhibit Bacterial Biofilm Formation

Marine Drugs ◽  
2018 ◽  
Vol 16 (8) ◽  
pp. 274 ◽  
Author(s):  
Anna Carbone ◽  
Barbara Parrino ◽  
Maria Cusimano ◽  
Virginia Spanò ◽  
Alessandra Montalbano ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Biofilm Formation ◽  
Microbial Growth ◽  
Bacterial Biofilm ◽  
Dependent Manner ◽  
Gram Negative ◽  
Ic50 Values ◽  
Planktonic Form ◽  
New Compounds ◽  
Dose Dependent

New thiazole nortopsentin analogues were conveniently synthesized and evaluated for their activity as inhibitors of biofilm formation of relevant Gram-positive and Gram-negative pathogens. All compounds were able to interfere with the first step of biofilm formation in a dose-dependent manner, showing a selectivity against the staphylococcal strains. The most active derivatives elicited IC50 values against Staphylococcus aureus ATCC 25923, ranging from 0.40–2.03 µM. The new compounds showed a typical anti-virulence profile, being able to inhibit the biofilm formation without affecting the microbial growth in the planktonic form.

scholarly journals Is lipopolysaccharide a factor in infectivity of Chlamydia trachomatis?

2008 ◽  
Vol 57 (3) ◽  
pp. 261-266 ◽  
Author(s):  
Sanaa Fadel ◽  
Adrian Eley
Keyword(s):  
Chlamydia Trachomatis ◽  
Epithelial Cells ◽  
Host Cell ◽  
Lipid A ◽  
Polymyxin B ◽  
Gram Negative Bacteria ◽  
Dependent Manner ◽  
Gram Negative ◽  
Major Surface ◽  
Dose Dependent

Lipopolysaccharide (LPS) is a major surface component of Chlamydia trachomatis, as with all Gram-negative bacteria. The effect of C. trachomatis LPS on C. trachomatis infectivity of human epithelial cells was investigated. C. trachomatis LPS and C. trachomatis LPS antibody significantly reduced infectivity, mostly in a dose-dependent manner. As the structure of LPS in C. trachomatis is simple and consists only of lipid A and 3-deoxy-d-manno-octulosonic acid (Kdo), we investigated whether lipid A or Kdo was inhibitory to chlamydial infectivity. Polymyxin B, as a lipid A inhibitor, and Kdo considerably reduced C. trachomatis infectivity. With all the LPS inhibitors used, there was greater inhibition against serovar E than serovar LGV. These results suggest a role for LPS in chlamydial infectivity. Elucidation of how LPS acts in infectivity and identification of host-cell receptors would help in understanding pathogenicity.

scholarly journals Secretion of proinflammatory cytokines by normal human melanocytes in response to lipopolysaccharide.

2011 ◽  
Vol 58 (4) ◽  
Author(s):  
Irena Tam ◽  
Krystyna Stępień
Keyword(s):  
Immune System ◽  
Inflammatory Cytokines ◽  
Proinflammatory Cytokines ◽  
Large Body ◽  
Dependent Manner ◽  
Skin Immune System ◽  
Human Melanocytes ◽  
Tnf Α ◽  
Normal Human ◽  
Dose Dependent

A large body of evidence suggests that epidermal melanocytes are an integral part of the skin immune system and can be considered immunocompetent cells. Recently, it has been reported that human melanocytes constitutively express Toll-like receptors and may be involved in the induction of several inflammatory cytokines. In the study the secretion of IL-1β, IL-6 and TNF-α by cultured normal melanocytes was investigated after stimulation with lipopolysaccharide. LPS increased the secretion of IL-1β in a dose-dependent manner. IL-1β stimulated release of IL-6 and TNF-α by melanocytes, whereas LPS activated production of TNF-α, but not of IL-6. These observations indicate that LPS can participate in the regulation of cytokine activity in normal human melanocytes and suggest that cytokines released by melanocytes could affect melanocytes themselves or/and other cells of the epidermis.

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