Immunomodulatory Responses Of Toll Like Receptors Against 2019nCoV

The present review discusses the immune signals via toll like receptors (TLRs) against 2019nCoV. We researched using different database, up to June 18th, 2020. All the included articles were published in English language. The outcome of this review, that some TLRs agonists or antagonists are progressed as drugs to combat and down regulating TLRs immune signals respectively. TLRs 3 and 4 recognized 2019nCoV spike protein through immune and molecular signals that leading to immune stimulation of pro-inflammatory cytokines and even the immune fever. While the TLRs7 and 8 recognized single-stranded ribonucleic acids (ssRNAs) leading to elevation of the tumour necrosis factor α (TNF-α), interleukin (IL)-6 and -12 levels. TLRs agonists or antagonists utilized as immunotherapeutic targets against 2019nCoV via TLRs signals. Chloroquine and hydroxychloroquine; the approval compounds for 2019nCoV therapy can be inhibiting the class II major histocompatibility complex molecules expression and antigen presentation and even immune suppressions of the pro-inflammatory cytokines profile.

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Expression and functionality study of 9 Toll-like receptors in drug-naïve non-affective first episode psychosis individuals: a 3-month study

10.21203/rs.3.rs-17979/v1 ◽

2020 ◽

Author(s):

Maria Juncal-Ruiz ◽

Laura Riesco-Davila ◽

Mariluz Ramirez-Bonilla ◽

Victor Ortiz-Garcia de la Foz ◽

Javier Vazquez-Bourgon ◽

...

Keyword(s):

Healthy Volunteers ◽

Inflammatory Cytokines ◽

Mononuclear Cells ◽

Immune Cell ◽

First Episode ◽

Toll Like Receptors ◽

Tnf Α ◽

Drug Naïve ◽

Lower Expression ◽

Pro Inflammatory Cytokines

Abstract Background: Toll-like receptors (TLRs) are a pivotal component of the innate immune system, which are expressed by various subsets of immune cell types, included central nervous system. There are few publications that have studied TLR expression and/or functionality in psychosis, of which most of them have been based on chronic schizophrenia individuals.Objectives: To compare the expression and functionality of 9TLRs in three peripheral blood mononuclear cells (PBMCs) (monocytes, B cells and T cells) within a sample of 33 drug-naïve FEP individuals and 26 healthy volunteers, at baseline and after 3-month of antipsychotic treatment.Methods: The expression of TLR1-9 was assessed by ﬂow cytometry. For the assessment of the TLR functionality (measured as intracellular production of IL-1β, IL-6 and TNF-α following TLR stimulation), cells collected in sodium heparin tubes were polyclonally stimulated for 18h with different agonists for human TLR1–9.Results: Patients showed a lower expression of TLR5 and TLR8 on the three PBMCs at baseline and after 3-month of treatment regarding healthy volunteers (all ps <0.01). We also found less production of some intracellular pro-inflammatory cytokines (especially TNF-α) after TLR stimulation in patients at both baseline and following the medication (all ps <0.01). We have not found differences in the intra-subject analyses after 3-month of treatment.Conclusions: Drug-naive patients with schizophrenia spectrum disorders show lower expression of specific TLR receptors as well as lower intracellular concentrations of some pro-inflammatory cytokines after TLR stimulation. These findings may be a consequence of an excessive cell stimulation via exogenous ligands (such as pathogens) and/or endogenous ligands (such as autoimmunity) in such a way that PBMCs could be exhausted to be activated in the in vitro analyses.

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Pro-Inflammatory Cytokines at Ultra-Low Dose Exert Anti-Inflammatory Effect In Vitro: A Possible Mode of Action Involving Sub-Micron Particles?

Dose-Response ◽

10.1177/1559325820961723 ◽

2020 ◽

Vol 18 (4) ◽

pp. 155932582096172

Author(s):

Ilaria Floris ◽

Thorsten Rose ◽

Juan Antonio Collado Rojas ◽

Kurt Appel ◽

Camille Roesch ◽

...

Keyword(s):

Inflammatory Cytokines ◽

Mode Of Action ◽

Inflammatory Diseases ◽

Resistive Pulse ◽

Tnf Α ◽

Anti Inflammatory ◽

Factor Α ◽

Pro Inflammatory Cytokines ◽

Inflammatory Effect

Tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) are pro-inflammatory cytokines involved in acute and chronic inflammatory diseases. Indeed, immunotherapy blocking these 2 cytokines has been developed. Micro-immunotherapy (MI) also uses ultra-low doses (ULD) of pro-inflammatory cytokines, impregnated on lactose-sucrose pillules, to counteract their overexpression. The study has been conducted with 2 objectives: examine the anti-inflammatory effect in vitro and the capacity of 2 unitary medicines, TNF-α (27 CH) and IL-1β (27 CH), to reduce the secretion of TNF-α in human primary monocytes and THP-1 cells differentiated with phorbol-12-myristate-13-acetate, after lipopolysaccharide (LPS) exposure; then, investigate the presence of particles possibly containing starting materials using tunable resistive pulse sensing technique. The results show that the unitary medicines, tested at 3 pillules concentrations (5.5, 11 and 22 mM), have reduced the secretion of TNF-α in both models by about 10−20% vs. vehicle control, depending on concentration. In this exploratory study, particles (150−1000 nm) have been detected in MI ULD-impregnated pillules and a hypothesis for MI medicines mode of action has been proposed. Conscious that more evaluations are necessary, authors are cautious in the conclusions because the findings described in the study are still limited, and future investigations may lead to different hypothesis.

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Pro-inflammatory Cytokines: Cellular and Molecular Drug Targets for Glucocorticoid-induced-osteoporosis via Osteocyte

Current Drug Targets ◽

10.2174/1389450119666180405094046 ◽

2018 ◽

Vol 20 (1) ◽

pp. 1-15 ◽

Cited By ~ 8

Author(s):

Tiantian Wang ◽

Xijie Yu ◽

Chengqi He

Keyword(s):

Gap Junctions ◽

Bone Metabolism ◽

Inflammatory Cytokines ◽

Drug Targets ◽

Bone Mineralization ◽

Synergistic Effects ◽

Osteocyte Apoptosis ◽

Tnf Α ◽

Factor Α ◽

Pro Inflammatory Cytokines

Glucocorticoids are widely used to treat varieties of allergic and autoimmune diseases, however, long-term application results in glucocorticoid-induced osteoporosis (GIOP). Inflammatory cytokines: tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) play important regulatory roles in bone metabolism, but their roles in GIOP remain largely unknown. Osteocytes can modulate the formation and function of both osteoblasts and osteoclasts, directly via gap junctions, or indirectly by transferring molecule signaling. Apoptotic osteocytes release RANKL, HMGB1 and pro-inflammatory cytokines to stimulate osteoclastogenesis. Moreover, osteocytes can secrete FGF23 to regulate bone metabolism. Exposure to high levels of GCs can drive osteocyte apoptosis and influence gap junctions, leading to bone loss. GCs treatment is regarded to produce more FGF23 to inhibit bone mineralization. GCs also disrupt the vascular to decrease osteocyte feasibility and mineral appositional rate, resulting in a decline in bone strength. Apoptotic bodies from osteocytes induced by GCs treatment can enhance production of TNF-α and IL-6. On the other hand, TNF-α and IL-6 show synergistic effects by altering osteocytes signaling towards osteoclasts and osteoblasts. In addition, TNF-α can induce osteocyte apoptosis and attribute to a worsened bone quality in GCs. IL-6 and osteocytes may interact with each other. Therefore, we hypothesize that GCs regulate osteocyteogenesis through TNF-α and IL-6, which are highly expressed around osteocyte undergoing apoptosis. In the present review, we summarized the roles of osteocytes in regulating osteoblasts and osteoclasts. Furthermore, the mechanism of GCs altered relationship between osteocytes and osteoblasts/osteoclasts. In addition, we discussed the roles of TNF-α and IL-6 in GIOP by modulating osteocytes. Lastly, we discussed the possibility of using pro-inflammatory signaling pathway as therapeutic targets to develop drugs for GIOP.

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Effect of Melittin on Metabolomic Profile and Cytokine Production in PMA-Differentiated THP-1 Cells

Vaccines ◽

10.3390/vaccines6040072 ◽

2018 ◽

Vol 6 (4) ◽

pp. 72 ◽

Cited By ~ 4

Author(s):

Abdulmalik Alqarni ◽

Valerie Ferro ◽

John Parkinson ◽

Mark Dufton ◽

David Watson

Keyword(s):

Inflammatory Cytokines ◽

Cell Activation ◽

Flash Chromatography ◽

System Response ◽

Macrophage Cell ◽

Tnf Α ◽

Immune System Response ◽

Factor Α ◽

Necrosis Factor ◽

Pro Inflammatory Cytokines

Melittin, the major active peptide of honeybee venom (BV), has potential for use in adjuvant immunotherapy. The immune system response to different stimuli depends on the secretion of different metabolites from macrophages. One potent stimulus is lipopolysaccharide (LPS), a component isolated from gram-negative bacteria, which induces the secretion of pro-inflammatory cytokines in macrophage cell cultures. This secretion is amplified when LPS is combined with melittin. In the present study, pure melittin was isolated from whole BV by flash chromatography to obtain pure melittin. The ability of melittin to enhance the release of tumour necrosis factor-α (TNF-α), Interleukin (IL-1β, IL-6, and IL-10) cytokines from a macrophage cell line (THP-1) was then assessed. The response to melittin and LPS, applied alone or in combination, was characterised by metabolic profiling, and the metabolomics results were used to evaluate the potential of melittin as an immune adjuvant therapy. The addition of melittin enhanced the release of inflammatory cytokines induced by LPS. Effective chromatographic separation of metabolites was obtained by liquid chromatography-mass spectrometry (LC-MS) using a ZIC-pHILIC column and an ACE C4 column. The levels of 108 polar and non-polar metabolites were significantly changed (p ˂ 0.05) following cell activation by the combination of LPS and melittin when compared to untreated control cells. Overall, the findings of this study suggested that melittin might have a potential application as a vaccine adjuvant.

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Expression and extracellular release of Trx80, the truncated form of thioredoxin, by TNF-α- and IL-1β-stimulated human synoviocytes from patients with rheumatoid arthritis

Clinical Science ◽

10.1042/cs20070067 ◽

2007 ◽

Vol 113 (3) ◽

pp. 149-155 ◽

Cited By ~ 12

Author(s):

Hervé Lemarechal ◽

Phillippe Anract ◽

Jean-Louis Beaudeux ◽

Dominique Bonnefont-Rousselot ◽

Ohvanesse G. Ekindjian ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Inflammatory Cytokines ◽

Protein Interactions ◽

Ex Vivo ◽

Truncated Form ◽

Experimental Conditions ◽

Extracellular Release ◽

Tnf Α ◽

Factor Α ◽

Pro Inflammatory Cytokines

Thioredoxin (Trx) plays several important roles, through changes to sulfhydryl reactions and protein interactions, in controlling cellular signalling processes in RA (rheumatoid arthritis). Trx80, the 10 kDa C-terminal truncated form of Trx, is a potent mitogenic cytokine and is involved in the Th1 response. In the present study, we have investigated the ability of synoviocytes from five RA patients to induce Trx80 after ex vivo stimulation by the pro-inflammatory cytokines IL-1β (interleukin-1β) and TNF-α (tumour necrosis factor-α) or by H2O2. Synoviocytes from five OA (osteoarthritis) patients were used as controls. Immunoprecipitation assays using two different antibodies showed that RA, but not OA, cells expressed intact Trx80 protein in culture even when not stimulated. Treatment with pro-inflammatory cytokines alone or in combination enhanced this basal production and induced the extracellular release of Trx80 by all of the RA cells tested. Under our experimental conditions, the rate of Trx80 release from RA cells was approx. 30% of the total Trx produced. In contrast, Trx80 was not detected in response to H2O2 in RA or OA synoviocyte lysates and their respective culture supernatants, indicating that the oxidative process induced by H2O2 in synoviocytes was unable to modify Trx80 release. Moreover, Trx80 induced synoviocyte proliferation as evaluated by [3H]thymidine incorporation. These results highlight the effect of the inflammatory process on the release of both Trx and Trx80 from RA synoviocytes, and suggest that the cytokine-induced increase in Trx80 cell release may constitute a link between inflammation and the immune system in RA.

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Inhibition of Pro-Inflammatory Cytokine Secretion by Select Antioxidants in Human Coronary Artery Endothelial Cells

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831/a000520 ◽

2020 ◽

Vol 90 (1-2) ◽

pp. 103-112 ◽

Cited By ~ 1

Author(s):

Michael J. Haas ◽

Marilu Jurado-Flores ◽

Ramadan Hammoud ◽

Victoria Feng ◽

Krista Gonzales ◽

...

Keyword(s):

Endothelial Cells ◽

Ascorbic Acid ◽

Coronary Artery ◽

Inflammatory Cytokines ◽

Inflammatory Cytokine ◽

Culture Media ◽

Cytokine Secretion ◽

Human Coronary Artery ◽

Tnf Α ◽

Pro Inflammatory Cytokines

Abstract. Inflammatory and oxidative stress in endothelial cells are implicated in the pathogenesis of premature atherosclerosis in diabetes. To determine whether high-dextrose concentrations induce the expression of pro-inflammatory cytokines, human coronary artery endothelial cells (HCAEC) were exposed to either 5.5 or 27.5 mM dextrose for 24-hours and interleukin-1β (IL-1β), interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor α (TNF α) levels were measured by enzyme immunoassays. To determine the effect of antioxidants on inflammatory cytokine secretion, cells were also treated with α-tocopherol, ascorbic acid, and the glutathione peroxidase mimetic ebselen. Only the concentration of IL-1β in culture media from cells exposed to 27.5 mM dextrose increased relative to cells maintained in 5.5 mM dextrose. Treatment with α-tocopherol (10, 100, and 1,000 μM) and ascorbic acid (15, 150, and 1,500 μM) at the same time that the dextrose was added reduced IL-1β, IL-6, and IL-8 levels in culture media from cells maintained at 5.5 mM dextrose but had no effect on IL-1β, IL-6, and IL-8 levels in cells exposed to 27.5 mM dextrose. However, ebselen treatment reduced IL-1β, IL-6, and IL-8 levels in cells maintained in either 5.5 or 27.5 mM dextrose. IL-2 and TNF α concentrations in culture media were below the limit of detection under all experimental conditions studied suggesting that these cells may not synthesize detectable quantities of these cytokines. These results suggest that dextrose at certain concentrations may increase IL-1β levels and that antioxidants have differential effects on suppressing the secretion of pro-inflammatory cytokines in HCAEC.

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Molecular Mechanisms of Curcumin in Neuroinflammatory Disorders: A Mini Review of Current Evidences

Endocrine Metabolic & Immune Disorders - Drug Targets ◽

10.2174/1871530319666181129103056 ◽

2019 ◽

Vol 19 (3) ◽

pp. 247-258 ◽

Cited By ~ 7

Author(s):

Mahsa Hatami ◽

Mina Abdolahi ◽

Neda Soveyd ◽

Mahmoud Djalali ◽

Mansoureh Togha ◽

...

Keyword(s):

Nitric Oxide ◽

English Language ◽

Molecular Mechanisms ◽

Randomized Clinical Trials ◽

Mitochondrial Dynamics ◽

Nuclear Factor Κb ◽

General Term ◽

Neuroinflammatory Disease ◽

Tnf Α ◽

Factor Α

Objective: Neuroinflammatory disease is a general term used to denote the progressive loss of neuronal function or structure. Many neuroinflammatory diseases, including Alzheimer’s, Parkinson’s, and multiple sclerosis (MS), occur due to neuroinflammation. Neuroinflammation increases nuclear factor-κB (NF-κB) levels, cyclooxygenase-2 enzymes and inducible nitric oxide synthase, resulting in the release of inflammatory cytokines, such as interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). It could also lead to cellular deterioration and symptoms of neuroinflammatory diseases. Recent studies have suggested that curcumin (the active ingredient in turmeric) could alleviate the process of neuroinflammatory disease. Thus, the present mini-review was conducted to summarize studies regarding cellular and molecular targets of curcumin relevant to neuroinflammatory disorders. Methods: A literature search strategy was conducted for all English-language literature. Studies that assessed the various properties of curcuminoids in respect of neuroinflammatory disorders were included in this review. Results: The studies have suggested that curcuminoids have significant anti- neuroinflammatory, antioxidant and neuroprotective properties that could attenuate the development and symptom of neuroinflammatory disorders. Curcumin can alleviate neurodegeneration and neuroinflammation through multiple mechanisms, by reducing inflammatory mediators (such as TNF-α, IL-1β, nitric oxide and NF-κB gene expression), and affect mitochondrial dynamics and even epigenetic changes. Conclusion: It is a promising subject of study in the prevention and management of the neuroinflammatory disease. However, controlled, randomized clinical trials are needed to fully evaluate its clinical potential.

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

Nutrients ◽

10.3390/nu11112794 ◽

2019 ◽

Vol 11 (11) ◽

pp. 2794 ◽

Cited By ~ 8

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.

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Modulation of ACE-2 mRNA by inflammatory cytokines in human thyroid cells: a pilot study

Endocrine ◽

10.1007/s12020-021-02807-w ◽

2021 ◽

Author(s):

Francesca Coperchini ◽

Gianluca Ricci ◽

Laura Croce ◽

Marco Denegri ◽

Rubina Ruggiero ◽

...

Keyword(s):

Inflammatory Cytokines ◽

Combination Treatment ◽

Primary Cultures ◽

Human Thyroid ◽

Thyroid Cell ◽

Mrna Levels ◽

Thyroid Cells ◽

Tnf Α ◽

Ifn Γ ◽

Pro Inflammatory Cytokines

Abstract Introduction Angiotensin-converting-enzyme-2 (ACE-2) was demonstrated to be the receptor for cellular entry of SARS-CoV-2. ACE-2 mRNA was identified in several human tissues and recently also in thyroid cells in vitro. Purpose Aim of the present study was to investigate the effect of pro-inflammatory cytokines on the ACE-2 mRNA levels in human thyroid cells in primary cultures. Methods Primary thyroid cell cultures were treated with IFN-γ and TNF-α alone or in combination for 24 h. ACE-2 mRNA levels were measured by RT-PCR. As a control, the levels of IFN-γ inducible chemokine (CXCL10) were measured in the respective cell culture supernatants. Results The mean levels of ACE-2 mRNA increased after treatment with IFN-γ and TNF-α in all the thyroid cell preparations, while the combination treatment did not consistently synergically increase ACE-2-mRNA. At difference, CXCL10 was consistently increased by IFN-γ and synergically further increased by the combination treatment with IFN-γ + TNF-α, with respect to IFN-γ alone. Conclusions The results of the present study show that IFN-γ and, to a lesser extent TNF-α consistently increase ACE-2 mRNA levels in NHT primary cultures. More interestingly, the combined stimulation (proven to be effective according to the synergic effect registered for CXCL10) produces different responses in terms of ACE-2 mRNA modulation. These results would suggest that elevated levels of pro-inflammatory cytokines could facilitate the entering of the virus in cells by further increasing ACE-2 expression and/or account for the different degree of severity of SARS-COV-2 infection. This hypothesis deserves to be confirmed by further specific studies.

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Effects of 14-weeks betaine supplementation on pro-inflammatory cytokines and hematology status in professional youth soccer players during a competition season: a double blind, randomized, placebo-controlled trial

Journal of the International Society of Sports Nutrition ◽

10.1186/s12970-021-00441-5 ◽

2021 ◽

Vol 18 (1) ◽

Author(s):

Hadi Nobari ◽

Jason M. Cholewa ◽

Jorge Pérez-Gómez ◽

Alfonso Castillo-Rodríguez

Keyword(s):

Inflammatory Cytokines ◽

Blood Cells ◽

Well Being ◽

Soccer Players ◽

Mean Corpuscular Hemoglobin ◽

Significant Group ◽

Youth Soccer ◽

Tnf Α ◽

Betaine Supplementation ◽

Pro Inflammatory Cytokines

Abstract Objective Systemic elevations in pro-inflammatory cytokines are a marker of non-functional over reaching, and betaine has been shown to reduce the secretion of pro-inflammatory cytokines in vitro. The aim of this study was to investigate the effects of betaine supplementation on tumor necrosis factor alpha (TNF-α), interleukins-1 beta (IL-1β), − 6 (IL-6) and the complete blood cell (CBC) count in professional youth soccer players during a competitive season. Methods Twenty-nine soccer players (age, 15.5 ± 0.3 years) were randomly divided into two groups based on playing position: betaine group (BG, n = 14, 2 g/day) or placebo group (PG, n = 15). During the 14-week period, training load was matched and well-being indicators were monitored daily. The aforementioned cytokines and CBC were assessed at pre- (P1), mid- (P2), and post- (P3) season. Results Significant (p < 0.05) group x time interactions were found for TNF-α, IL-1β, and IL-6. These variables were lower in the BG at P2 and P3 compared to P1, while IL-1β was greater in the PG at P3 compared to P1 (p = 0.033). The CBC count analysis showed there was significant group by time interactions for white blood cells (WBC), red blood cells (RBC), hemoglobin (Hb), and mean corpuscular hemoglobin concentration (MCHC). WBC demonstrated increases at P3 compared to P2 in PG (p = 0.034); RBC was less at P3 compared to P1 in BG (p = 0.020); Hb was greater at P2 compared to P1, whilst it was less at P3 compared to P3 for both groups. MCHC was greater at P3 and P2 compared to P1 in BG, whereas MCHC was significantly lower at P3 compared to P2 in the PG (p = 0.003). Conclusion The results confirmed that 14 weeks of betaine supplementation prevented an increase in pro-inflammatory cytokines and WBC counts. It seems that betaine supplementation may be a useful nutritional strategy to regulate the immune response during a fatiguing soccer season.

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