scholarly journals Caspase-11 Noncanonical Inflammasome: A Novel Key Player in Murine Models of Neuroinflammation and Multiple Sclerosis

2021 ◽  
pp. 1-9
Author(s):  
Young-Su Yi
Keyword(s):  
Multiple Sclerosis ◽  
Inflammatory Responses ◽  
Protein Complexes ◽  
Murine Models ◽  
Intracellular Protein ◽  
Inflammatory Molecules ◽  
Human Caspase ◽  
Receptor Family ◽  
Inflammatory Autoimmune Diseases ◽  
Pro Inflammatory Cytokines

Inflammasomes are intracellular protein complexes consisting of the pattern recognition receptors and inflammatory molecules in the inflamed cells. In response to various ligands, inflammasomes play a pivotal role to execute the inflammatory responses by inducing the pyroptosis and the secretion of pro-inflammatory cytokines, interleukin (IL)-1β, and IL-18. Unlike canonical inflammasomes, including NOD-like receptor family inflammasomes, such as NLRP1, NLRP3, NLRC4, and absence in melanoma 2 inflammasomes, noncanonical inflammasomes, such as mouse caspase-11 and human caspase-4/5 were recently discovered, and their roles in the inflammatory responses have been poorly understood. However, emerging studies have been successfully demonstrating the regulatory roles of these noncanonical inflammasomes on inflammatory responses and the pathogenesis of inflammatory/autoimmune diseases. This review summarizes and discusses the recent studies investigating the regulatory roles of the caspase-11 noncanonical inflammasome in neuroinflammation and the pathogenesis of multiple sclerosis (MS), which provides the insight for the validation of caspase-11 noncanonical inflammasome to develop novel and promising therapeutics for MS.

scholarly journals Editorial of Special Issue “Regulatory Roles of Inflammasomes in Human Diseases”

2021 ◽  
Vol 22 (6) ◽  
pp. 3008
Author(s):  
Young-Su Yi ◽  
Miyong Yun
Keyword(s):  
Drug Targets ◽  
Inflammatory Responses ◽  
Protein Complexes ◽  
The Body ◽  
Human Diseases ◽  
Inflammasome Activation ◽  
Special Issue ◽  
Intracellular Protein ◽  
Inflammatory Molecules ◽  
Pro Inflammatory Cytokines

Inflammation is an innate immunity protecting the body from pathogens and cellular damages and comprises two steps; 1) priming (preparatory step) and triggering (activation step). The key feature of the triggering step is the activation of inflammasomes that are intracellular protein complexes consisting of pattern recognition receptors and inflammatory molecules. Inflammasomes are activated in response to various ligands, leading to the caspase-1-mediated maturation and secretion of pro-inflammatory cytokines, IL-1β and IL-18 and the gasdermin D-mediated pyroptosis, an inflammatory form of cell death. Previous studies have demonstrated that inflammasome activation is a key determinant of inflammatory responses and many human diseases; therefore, inflammasomes have been attracted much attention as critical drug targets to prevent and treat various human diseases.

scholarly journals Punicalagin Prevents Inflammation in LPS-Induced RAW264.7 Macrophages by Inhibiting FoxO3a/Autophagy Signaling Pathway

Nutrients ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 2794 ◽  
Author(s):  
Cao ◽  
Chen ◽  
Ren ◽  
Zhang ◽  
Tan ◽  
...  
Keyword(s):  
Western Blot ◽  
Signaling Pathway ◽  
Inflammatory Cytokines ◽  
Blot Analysis ◽  
Western Blot Analysis ◽  
Inflammatory Responses ◽  
Raw264.7 Macrophages ◽  
Tnf Α ◽  
Autophagy Inhibition ◽  
Pro Inflammatory Cytokines

Punicalagin, a hydrolysable tannin of pomegranate juice, exhibits multiple biological effects, including inhibiting production of pro-inflammatory cytokines in macrophages. Autophagy, an intracellular self-digestion process, has been recently shown to regulate inflammatory responses. In this study, we investigated the anti-inflammatory potential of punicalagin in lipopolysaccharide (LPS) induced RAW264.7 macrophages and uncovered the underlying mechanisms. Punicalagin significantly attenuated, in a concentration-dependent manner, LPS-induced release of NO and decreased pro-inflammatory cytokines TNF-α and IL-6 release at the highest concentration. We found that punicalagin inhibited NF-κB and MAPK activation in LPS-induced RAW264.7 macrophages. Western blot analysis revealed that punicalagin pre-treatment enhanced LC3II, p62 expression, and decreased Beclin1 expression in LPS-induced macrophages. MDC assays were used to determine the autophagic process and the results worked in concert with Western blot analysis. In addition, our observations indicated that LPS-induced releases of NO, TNF-α, and IL-6 were attenuated by treatment with autophagy inhibitor chloroquine, suggesting that autophagy inhibition participated in anti-inflammatory effect. We also found that punicalagin downregulated FoxO3a expression, resulting in autophagy inhibition. Overall these results suggested that punicalagin played an important role in the attenuation of LPS-induced inflammatory responses in RAW264.7 macrophages and that the mechanisms involved downregulation of the FoxO3a/autophagy signaling pathway.

scholarly journals Flavonoids: Nutraceuticals for Rheumatic Diseases via Targeting of Inflammasome Activation

2021 ◽  
Vol 22 (2) ◽  
pp. 488
Author(s):  
Young-Su Yi
Keyword(s):  
Rheumatic Diseases ◽  
Fruits And Vegetables ◽  
Inflammatory Responses ◽  
Protein Complexes ◽  
Cellular Damage ◽  
Inflammatory Rheumatic Diseases ◽  
Inflammasome Activation ◽  
Central Feature ◽  
Inflammatory Protein ◽  
Anti Inflammatory

Inflammation, an innate immune response that prevents cellular damage caused by pathogens, consists of two successive mechanisms, namely priming and triggering. While priming is an inflammation-preparation step, triggering is an inflammation-activation step, and the central feature of triggering is the activation of inflammasomes and intracellular inflammatory protein complexes. Flavonoids are natural phenolic compounds predominantly present in plants, fruits, and vegetables and are known to possess strong anti-inflammatory activities. The anti-inflammatory activity of flavonoids has long been demonstrated, with the main focus on the priming mechanisms, while increasing numbers of recent studies have redirected the research focus on the triggering step, and studies have reported that flavonoids inhibit inflammatory responses and diseases by targeting inflammasome activation. Rheumatic diseases are systemic inflammatory and autoimmune diseases that primarily affect joints and connective tissues, and they are associated with numerous deleterious effects. Here, we discuss the emerging literature on the ameliorative role of flavonoids targeting inflammasome activation in inflammatory rheumatic diseases.

scholarly journals Mutant glucocorticoid receptor binding elements on the interleukin-6 promoter regulate dexamethasone effects

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Wen-Teng Chang ◽  
Ming-Yuan Hong ◽  
Chien-Liang Chen ◽  
Chi-Yuan Hwang ◽  
Cheng-Chieh Tsai ◽  
...  
Keyword(s):  
Binding Sites ◽  
Inflammatory Diseases ◽  
Inducible Promoter ◽  
Transcriptional Factor ◽  
Factor Binding ◽  
Inflammatory Processes ◽  
Nuclear Receptor Family ◽  
Specificity Protein ◽  
Receptor Family ◽  
Pro Inflammatory Cytokines

Abstract Background Glucocorticoids (GCs) have been extensively used as essential modulators in clinical infectious and inflammatory diseases. The GC receptor (GR) is a transcription factor belonging to the nuclear receptor family that regulates anti-inflammatory processes and releases pro-inflammatory cytokines, such as interleukin (IL)-6. Results Five putative GR binding sites and other transcriptional factor binding sites were identified on theIL-6 promoter, and dexamethasone (DEX) was noted to reduce the lipopolysaccharide (LPS)-induced IL-6 production. Among mutant transcriptional factor binding sites, nuclear factor-kappa B (NF-κB), activator protein (AP)-1, and specificity protein (Sp)1–2 sites reduced basal and LPS-induced IL-6 promoter activities through various responses. The second GR binding site (GR2) was noted to play a crucial role in both basal and inducible promoter activities in LPS-induced inflammation. Conclusions We concluded that selective GR2 modulator might exert agonistic and antagonistic effects and could activate crucial signaling pathways during the LPS-stimulated inflammatory process.

scholarly journals Peptide VSAK maintains tissue glucose uptake and attenuates pro-inflammatory responses caused by LPS in an experimental model of the systemic inflammatory response syndrome: a PET study

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ismael Luna-Reyes ◽  
Eréndira G. Pérez-Hernández ◽  
Blanca Delgado-Coello ◽  
Miguel Ángel Ávila-Rodríguez ◽  
Jaime Mas-Oliva
Keyword(s):  
Systemic Inflammatory Response Syndrome ◽  
Inflammatory Response ◽  
Glucose Uptake ◽  
Inflammatory Responses ◽  
Serum Levels ◽  
Systemic Inflammatory Response ◽  
Positron Emission ◽  
Inflammatory Molecules ◽  
Circulating Levels ◽  
Lps Treatment

AbstractThe present investigation using Positron Emission Tomography shows how peptide VSAK can reduce the detrimental effects produced by lipopolysaccharides in Dutch dwarf rabbits, used to develop the Systemic Inflammatory Response Syndrome (SIRS). Animals concomitantly treated with lipopolysaccharides (LPS) and peptide VSAK show important protection in the loss of radiolabeled-glucose uptake observed in diverse organs when animals are exclusively treated with LPS. Treatment with peptide VSAK prevented the onset of changes in serum levels of glucose and insulin associated with the establishment of SIRS and the insulin resistance-like syndrome. Treatment with peptide VSAK also allowed an important attenuation in the circulating levels of pro-inflammatory molecules in LPS-treated animals. As a whole, our data suggest that peptide VSAK might be considered as a candidate in the development of new therapeutic possibilities focused on mitigating the harmful effects produced by lipopolysaccharides during the course of SIRS.

scholarly journals Cystine reduces tight junction permeability and intestinal inflammation induced by oxidative stress in Caco-2 cells

Amino Acids ◽  
2021 ◽  
Author(s):  
Tatsuya Hasegawa ◽  
Ami Mizugaki ◽  
Yoshiko Inoue ◽  
Hiroyuki Kato ◽  
Hitoshi Murakami
Keyword(s):  
Oxidative Stress ◽  
Tight Junction ◽  
Mrna Expression ◽  
Inflammatory Cytokines ◽  
Inflammatory Responses ◽  
Intestinal Barrier ◽  
Barrier Dysfunction ◽  
Whole Cells ◽  
Intestinal Barrier Dysfunction ◽  
Pro Inflammatory Cytokines

AbstractIntestinal oxidative stress produces pro-inflammatory cytokines, which increase tight junction (TJ) permeability, leading to intestinal and systemic inflammation. Cystine (Cys2) is a substrate of glutathione (GSH) and inhibits inflammation, however, it is unclear whether Cys2 locally improves intestinal barrier dysfunction. Thus, we investigated the local effects of Cys2 on oxidative stress-induced TJ permeability and intestinal inflammatory responses. Caco-2 cells were cultured in a Cys2-supplemented medium for 24 h and then treated with H2O2 for 2 h. We assessed TJ permeability by measuring transepithelial electrical resistance and the paracellular flux of fluorescein isothiocyanate–dextran 4 kDa. We measured the concentration of Cys2 and GSH after Cys2 pretreatment. The mRNA expression of pro-inflammatory cytokines was assessed. In addition, the levels of TJ proteins were assessed by measuring the expression of TJ proteins in the whole cells and the ratio of TJ proteins in the detergent-insoluble fractions to soluble fractions (IS/S ratio). Cys2 treatment reduced H2O2-induced TJ permeability. Cys2 did not change the expression of TJ proteins in the whole cells, however, suppressed the IS/S ratio of claudin-4. Intercellular levels of Cys2 and GSH significantly increased in cells treated with Cys2. Cys2 treatment suppressed the mRNA expression of pro-inflammatory cytokines, and the mRNA levels were significantly correlated with TJ permeability. In conclusion, Cys2 treatment locally reduced oxidative stress-induced intestinal barrier dysfunction possively due to the mitigation of claudin-4 dislocalization. Furthermore, the effect of Cys2 on the improvement of intestinal barrier function is related to the local suppression of oxidative stress-induced pro-inflammatory responses.

scholarly journals Geongangbuja-Tang Decoction and Its Active Ingredient, Aconiti Lateralis Radix Preparata, Exerts Inhibitory Effects on Heat Stress-Induced Inflammation in Mice

2021 ◽  
Vol 11 (15) ◽  
pp. 6902
Author(s):  
Eugene Huh ◽  
Wonil Lee ◽  
Yujin Choi ◽  
Tae Hee Lee ◽  
Myung Sook Oh
Keyword(s):  
Heat Stress ◽  
Energy Metabolism ◽  
Inflammatory Cytokines ◽  
Hpa Axis ◽  
Inflammatory Responses ◽  
Heat Exposure ◽  
Mouse Serum ◽  
Dependent Manner ◽  
Active Constituent ◽  
Pro Inflammatory Cytokines

Heat stress induces the hypothalamic-pituitary-adrenal (HPA) axis activation, influences biological responses, and reduces energy metabolism. Geongangbuja-tang (GBT) and its components, Zingiberis Rhizoma (ZOR) and Aconiti Lateralis Radix Preparata (ALRP) have been used to induce energy metabolism; however, the effects of GBT and its ingredients on heat-induced inflammatory responses have not yet been investigated. In this study, we performed an open-field test to evaluate locomotor activity in mice. To assess the effects of GBT and its ingredients on inflammation, the protein levels of c-fos, pro-inflammatory cytokines, and cortisol were measured in the mouse hypothalamus and serum. The results showed that GBT alleviated locomotive activity and reduced c-fos levels in a dose-dependent manner under the heat exposure. After investigating the active constituent of GBT, we found that compared to GBT and ZOR, ALRP significantly suppressed c-fos expression under heat stress. Subsequently, ALRP decreased the expression of pro-inflammatory cytokines, such as interleukin-9 and -13 and prostaglandin, under the heat stress in the mouse hypothalamus. Moreover, treatment with ALRP inhibited cortisol secretion in the mouse serum following heat exposure. These results indicate that GBT and its active component, ALRP, could be the thermoregulatory agents that regulate the HPA axis.

An overview of the α4β1 integrin and the potential therapeutic role of its antagonists

2021 ◽  
Vol 28 ◽  
Author(s):  
Elenilze F. B. Ferreira ◽  
Luciane B. Silva ◽  
Josiane V. Cruz ◽  
Pedro H. F. Araújo ◽  
Njogu M. Kimani ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Monoclonal Antibody ◽  
Extracellular Matrix ◽  
Inflammatory Responses ◽  
Cellular Responses ◽  
Tumour Invasion ◽  
Potential Therapeutic Role ◽  
Integrin Antagonists ◽  
Inside Out

: This article presents a simplified view of integrins with emphasis on the α4 (α4β1/VLA-4) integrin. Integrins are heterodimeric proteins expressed on the cell surface of leukocytes that participate in a wide variety of functions, such as survival, growth, differentiation, migration, inflammatory responses, tumour invasion, among others. When the extracellular matrix is degraded or deformed, cells are forced to undergo responsive changes that influence remodelling during physiological and pathological events. Integrins recognize these changes and trigger a series of cellular responses, forming a physical connection between the interior and the outside of the cell. The communication of integrins through the plasma membrane occurs in both directions, from the extracellular to the intracellular (outside-in) and from the intracellular to the extracellular (inside-out). Integrins are valid targets for antibodies and small molecule antagonists. One example is the monoclonal antibody natalizumab, marketed under the name of TYSABRI®, used in the treatment of recurrent multiple sclerosis, which inhibits the adhesion of α4 integrin to its counter-receptor. α4β1 Integrin antagonists are summarized here and their utility as therapeutics discussed.

scholarly journals The Biology of ‘Risk-On’. Decreasing Inflammatory and Stress Responses on a London Trading Floor

2018 ◽  
Author(s):  
N. Z. Xie ◽  
L. Page ◽  
D. A. Granger ◽  
J. M. Coates
Keyword(s):  
Risk Taking ◽  
Stress Responses ◽  
Inflammatory Responses ◽  
Sickness Behaviour ◽  
Market Prices ◽  
Highly Sensitive ◽  
Natural Settings ◽  
City Of London ◽  
The City ◽  
Pro Inflammatory Cytokines

AbstractHuman physiological arousal is highly sensitive to information and uncertainty. Little is known, however, about how to measure information in natural settings, nor about which physiological systems respond to it. Financial market prices, and their volatility, present a convenient measure of informational load. Here we report on a study into the physiological response of traders in the City of London during a period of extreme, but declining, volatility. We sampled salivary cortisol, the main stress hormone, and the pro-inflammatory cytokines, IL-1β, IL-6, IL-8, and TNF-α three times a day for two weeks. We found that average daily cortisol levels tracked closely an index of equity and bond volatility, as did levels of IL-1β. Within-day cortisol and IL-1β levels also tracked one hour lagged volatility. Interestingly, the cascade of endocrine and immunological changes was initiated by IL-1β, the first responder of the stress and inflammatory responses. Our results have implications for finance because chronic stress and the immune response known as ‘sickness behaviour’ could have powerful effects on risk-taking and market stability.

scholarly journals Macrophage-Biomimetic Porous Se@SiO2 Nanocomposites For “Dual Model” Immunotherapy Against Inflammatory Osteolysis

2021 ◽  
Author(s):  
Cheng Ding ◽  
Chuang Yang ◽  
Tao Cheng ◽  
Xingyan Wang ◽  
Qiaojie Wang ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Inflammatory Responses ◽  
Total Joint Replacement ◽  
Major Complication ◽  
Dual Model ◽  
Joint Replacement Surgery ◽  
Pro Inflammatory Cytokines ◽  
Macrophage Membrane

Abstract Background：Inflammatory osteolysis is a major complication of total joint replacement surgery that can cause prosthesis failure and necessitate revision surgery. Macrophages are key effector immune cells in inflammatory responses, but excessive M1-polarization of dysfunctional macrophages leads to the secretion of pro-inflammatory cytokines and severe loss of bone tissue. Here, we report the development of macrophage-biomimetic porous SiO2-coated ultrasmall Se particles (Porous Se@SiO2 nanospheres) for the management of inflammatory osteolysis. Results: Macrophage-membrane-coated porous Se@SiO2 nanospheres(M-Se@SiO2) can attenuate lipopolysaccharide (LPS)-induced inflammatory osteolysis by a dual-immunomodulatory effect. As macrophage membrane decoys, these nanoparticles reduce toxin levels and neutralize pro-inflammatory cytokines. Moreover, the release of Se can induce the polarization of macrophages toward the anti-inflammatory M2-phenotype. These effects are mediated via the inhibition of p65, p38, and extracellular signal-regulated kinase(ERK) signaling. Additionally, the immune environment created by M-Se@SiO2 reduces the inhibition of osteogenic differentiation caused by pro-inflammation cytokines, confirmed through in vitro and in vivo experiments.Conclusion: Our findings suggest that M-Se@SiO2 has an immunomodulatory role in LPS-induced inflammation and bone remodeling, which demonstrates that M-Se@SiO2 is a promising engineered nano-platform for the treatment of osteolysis arising after arthroplasty.

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