scholarly journals Attenuating Immune Response of Macrophage by Enhancing Hydrophilicity of Ti Surface

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Xiaohan Dai ◽  
Yan Wei ◽  
Xuehui Zhang ◽  
Song Meng ◽  
Xiaoju Mo ◽  
...  
Keyword(s):  
Immune Response ◽  
Cell Formation ◽  
Underlying Mechanism ◽  
Immunomodulatory Activity ◽  
Inflammatory Factor ◽  
Surface Hydrophilicity ◽  
Raw264.7 Macrophages ◽  
Assay Result

Immune responses can determine thein vivofate of implanted materials. The strategy for developing implants has shifted towards using materials with immunomodulatory activity. However, the immunoregulatory effect of hydrophilicity of titanium surface on the macrophage behavior and its underlying mechanism remain poorly understood. Here, the Ti surface hydrophilicity-dependent behavior of murine RAW264.7 macrophages was investigatedin vitro. Two laboratory models with significantly different surface hydrophilicity and similar roughness were established with Ti-polished and Ti-H2O2surfaces. The results of cell morphology observation showed that the Ti-H2O2surface yielded enhanced cell adhesion and less multinucleated cell formation. CCK-8 assay indicated that the growth rate of macrophage on Ti-H2O2surface is higher than that of Ti-polished. ELISA assay result revealed lower level of proinflammatory factor TNF-αand higher level of anti-inflammatory factor IL-10 on the Ti-H2O2surface compared to Ti-polished. Subsequently, immunofluorescence and western blotting analysis showed that activation of the NF-κB-TNF-αpathway might be involved in the modulation of the immune response by surface hydrophilicity. Together, these results suggested that relative high hydrophilic Ti surface might attenuate the immune response of macrophage by activating NF-κB signaling. These findings could provide new insights into designing implant devices for orthopedic applications.

scholarly journals Effect of oral administration of Lactobacillus paracasei L9 on mouse systemic immunity and the immune response in the intestine

2016 ◽  
Vol 68 (2) ◽  
pp. 311-318 ◽  
Author(s):  
Yuanbo Zhu ◽  
Jun Zhu ◽  
Liang Zhao ◽  
Ming Zhang ◽  
Huiyuan Guo ◽  
...  
Keyword(s):  
Immune Response ◽  
Probiotic Strain ◽  
Peritoneal Macrophages ◽  
Lactobacillus Paracasei ◽  
Immunomodulatory Activity ◽  
Systemic Immunity ◽  
Th1 Polarization ◽  
Igg Level

A probiotic strain Lactobacillus paracasei L9,which was isolated from human intestine, was investigated for its immunomodulatory activity in vivo. Results showed that L9 improved systemic immunity by enhancing the phagocytic activity of peritoneal macrophages, the proliferation ratio of splenocytes, the IgG level in the serum and the level of IgA in the mucosa. Further, L9induced theTh1-polarized immune response by elevating the IFN-?/IL-4 ratio in the mucosa. This effect was confirmed by the enhanced IL-12-inducing activity of macrophages after in vitro stimulation of L9. Also detected was increased expression of TLR-2mRNA in the mucosa. We predict that L9 could enhance innate immunity by activating TLR-2 in the mucosa, and enhance acquired immunity by promoting Th1 polarization through induced production of IL-12 by macrophages.

scholarly journals Natural Polyphenols as Immunomodulators to Rescue Immune Response Homeostasis: Quercetin as a Research Model against Severe COVID-19

Molecules ◽  
2021 ◽  
Vol 26 (19) ◽  
pp. 5803
Author(s):  
Roberta Bernini ◽  
Francesca Velotti
Keyword(s):  
Immune Response ◽  
Asymptomatic Infection ◽  
Immunomodulatory Activity ◽  
Research Model ◽  
Health Crisis ◽  
Therapeutic Drugs ◽  
Immunological Mechanisms ◽  
Relevant Role

The COVID-19 pandemic is caused by SARS-CoV-2 and is leading to the worst health crisis of this century. It emerged in China during late 2019 and rapidly spread all over the world, producing a broad spectrum of clinical disease severity, ranging from asymptomatic infection to death (4.3 million victims so far). Consequently, the scientific research is devoted to investigating the mechanisms of COVID-19 pathogenesis to both identify specific therapeutic drugs and develop vaccines. Although immunological mechanisms driving COVID-19 pathogenesis are still largely unknown, new understanding has emerged about the innate and adaptive immune responses elicited in SARS-CoV-2 infection, which are mainly focused on the dysregulated inflammatory response in severe COVID-19. Polyphenols are naturally occurring products with immunomodulatory activity, playing a relevant role in reducing inflammation and preventing the onset of serious chronic diseases. Mainly based on data collected before the appearance of SARS-CoV-2, polyphenols have been recently suggested as promising agents to fight COVID-19, and some clinical trials have already been approved with polyphenols to treat COVID-19. The aim of this review is to analyze and discuss the in vitro and in vivo research on the immunomodulatory activity of quercetin as a research model of polyphenols, focusing on research that addresses issues related to the dysregulated immune response in severe COVID-19. From this analysis, it emerges that although encouraging data are present, they are still insufficient to recommend polyphenols as potential immunomodulatory agents against COVID-19.

Extraction, Characterization and Immunological Activity of Polysaccharides from Cynomorium songaricum Rupr.

2021 ◽  
Vol 11 (8) ◽  
pp. 1543-1554
Author(s):  
Min Li ◽  
Jianhua Yang ◽  
Junping Hu
Keyword(s):  
Inflammatory Cytokines ◽  
Phagocytic Activity ◽  
Active Component ◽  
Immunomodulatory Activity ◽  
Immunological Activity ◽  
Raw264.7 Macrophages ◽  
Immunosuppressed Mice

Cynomorium songaricum Rupr. (CSP) have been used widely in TCM for many years, polysaccharides from CSP are main active component. In our previous research, we found that CSP play a role of immunomodulatory activity in vitro, but its mechanisms and in vivo immunomodulatory activity hadn’t been explored. In present study, we firstly extracted CSP and identified two new fractions CSP-a, CSP-b. To assess the immunomodulatory activity of CSP in vivo, cyclophosphamide (CTX)-induced immunosuppressed mice models were generated and then treated with CSP. The results demonstrated that CSP could improve thymus and spleen indices, phagocytic and clearance index, serum hemolysin, inflammatory cytokines productions in serum. To explore the mechanisms of CSP, CSP-a, CSP-b, RAW264.7 macrophages were used to evaluate the immunomodulatory activity in vitro, the results demonstrated that CSP, CSP-a, CSP-b can induce macrophage proliferation, enhance the phagocytic activity and increase cytokines expression. CSP, CSP-a, CSP-b possessed the immunomodulatory activity by inducing the phosphorylation of MAPKs. This study suggested that CSP may be useful for lessening chemotherapy-induced immunosuppression and proposed the basis for the clinical application of CSP.

scholarly journals Ethyl Caffeate Ameliorates Collagen-Induced Arthritis by Suppressing Th1 Immune Response

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Shikui Xu ◽  
Aixue Zuo ◽  
Zengjun Guo ◽  
Chunping Wan
Keyword(s):  
Immune Response ◽  
Therapeutic Potential ◽  
Underlying Mechanism ◽  
Pcr Analysis ◽  
Collagen Induced Arthritis ◽  
Th1 Cell ◽  
Intracellular Cytokines ◽  
Th1 Immune Response

The present study was designed to assess the antiarthritic potential of ECF in collagen-induced arthritis (CIA) and explore its underlying mechanism. Methods. In vitro, lymphocyte proliferation assay was measured by CCK-8 kit. In vivo, the therapeutic potential of ECF on CIA was investigated; surface marker, Treg cell, and intracellular cytokines (IL-17A and IFN-γ) were detected by flow cytometry. Th1 cell differentiation assay was performed, and mRNA expression in interferon-γ-related signaling was examined by q-PCR analysis. Results. In vitro, ECF markedly inhibited the proliferation of splenocytes in response to ConA and anti-CD3. In vivo, ECF treatment reduced the severity of CIA, inhibited IFN-γ and IL-6 secretion, and decreased the proportion of CD11b+Gr-1+ splenic neutrophil. Meanwhile, ECF treatment significantly inhibited the IFN-γ expression in CD4+T cell without obviously influencing the development of Th17 cells and T regulatory cells. In vitro, ECF suppressed the differentiation of naive CD4+ T cells into Th1. Furthermore, ECF intensely blocked the transcriptional expression in interferon-γ-related signaling, including IFN-γ, T-bet, STAT1, and STAT4. Conclusion. Our results indicated that ECF exerted antiarthritic potential in collagen-induced arthritis by suppressing Th1 immune response and interferon-γ-related signaling.

scholarly journals GSDMD-Mediated Cardiomyocyte Pyroptosis Promotes Myocardial I/R Injury

2021 ◽  
Author(s):  
Huairui Shi ◽  
Yang Gao ◽  
Zhen Dong ◽  
Ji'e Yang ◽  
Rifeng Gao ◽  
...  
Keyword(s):  
Human Peripheral Blood ◽  
Myocardial Infarct ◽  
Ischemia Reperfusion ◽  
Serum Levels ◽  
Underlying Mechanism ◽  
Myocardial Infarct Size ◽  
Inflammatory Factor ◽  
St Segment Elevation

Rationale: Pyroptosis is a morphologically and mechanistically distinct form of cell death and is characterized by gasdermin D (GSDMD) or gasdermin E (GSDME)-mediated necrosis with excessive inflammatory factor release. Cardiomyocyte necrosis and inflammation play key roles in the pathophysiology of myocardial ischemia/reperfusion (I/R) injury. However, whether cardiomyocytes undergo pyroptosis and the underlying mechanism in myocardial I/R injury remain unclear. Objective: We aimed to investigate the role of pyroptosis in myocardial I/R injury. Methods and Results: In vivo and in vitro experiments were used to investigate pyroptosis of cardiomyocyte and the associated mechanisms during I/R injury. Wild-type (WT), Myh6-Cre and cardiomyocyte-specific GSDMD-deficient (GSDMD-CKO) male mice were subjected to I/R. Human peripheral blood samples were collected from STEMI (acute ST-segment-elevation myocardial infarction) patients or control patients at 0, 1 and 24 h after PCI (percutaneous coronary intervention) in our department. The serum levels of GSDMD were measured by ELISA. H/R (hypoxia/reoxygenation) induced cardiomyocyte pyroptosis and the release of mature IL-18 but not IL-1β, which mechanistically resulted from GSDMD cleavage by caspase-11 in cardiomyocytes. Furthermore, GSDMD gene deletion blocked H/R-induced cardiomyocyte pyroptosis and IL-18 release. GSDMD and its pyroptosis-inducing N-terminal fragment (GSDMD-N) were upregulated in myocardial tissues after I/R injury. Immunofluorescence analysis showed that GSDMD was mainly localized in cardiomyocytes. GSDMD deficiency in cardiomyocytes significantly reduced the I/R-induced myocardial infarct size. Moreover, increased GSDMD serum levels were detected in patients exhibiting I/R injury 1 h after PCI for STEMI. Conclusions: Our results show that GSDMD-mediated cardiomyocyte pyroptosis is a key event during myocardial I/R injury and that the caspase-11/GSDMD pathway may be essential to this process. Additionally, GSDMD inhibition significantly reduces cardiomyocyte pyroptosis and I/R-induced myocardial injury.

scholarly journals GCH1 induces immunosuppression through metabolic reprogramming and IDO1 upregulation in triple-negative breast cancer

2021 ◽  
Vol 9 (7) ◽  
pp. e002383
Author(s):  
Jin-Li Wei ◽  
Si-Yu Wu ◽  
Yun-Song Yang ◽  
Yi Xiao ◽  
Xi Jin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Molecular Taxonomy ◽  
Underlying Mechanism ◽  
Metabolic Reprogramming ◽  
Sequencing Data ◽  
Aryl Hydrocarbon

PurposeRegulatory T cells (Tregs) heavily infiltrate triple-negative breast cancer (TNBC), and their accumulation is affected by the metabolic reprogramming in cancer cells. In the present study, we sought to identify cancer cell-intrinsic metabolic modulators correlating with Tregs infiltration in TNBC.Experimental designUsing the RNA-sequencing data from our institute (n=360) and the Molecular Taxonomy of Breast Cancer International Consortium TNBC cohort (n=320), we calculated the abundance of Tregs in each sample and evaluated the correlation between gene expression levels and Tregs infiltration. Then, in vivo and in vitro experiments were performed to verify the correlation and explore the underlying mechanism.ResultsWe revealed that GTP cyclohydrolase 1 (GCH1) expression was positively correlated with Tregs infiltration and high GCH1 expression was associated with reduced overall survival in TNBC. In vivo and in vitro experiments showed that GCH1 increased Tregs infiltration, decreased apoptosis, and elevated the programmed cell death-1 (PD-1)-positive fraction. Metabolomics analysis indicated that GCH1 overexpression reprogrammed tryptophan metabolism, resulting in L-5-hydroxytryptophan (5-HTP) accumulation in the cytoplasm accompanied by kynurenine accumulation and tryptophan reduction in the supernatant. Subsequently, aryl hydrocarbon receptor, activated by 5-HTP, bound to the promoter of indoleamine 2,3-dioxygenase 1 (IDO1) and thus enhanced the transcription of IDO1. Furthermore, the inhibition of GCH1 by 2,4-diamino-6-hydroxypyrimidine (DAHP) decreased IDO1 expression, attenuated tumor growth, and enhanced the tumor response to PD-1 blockade immunotherapy.ConclusionsTumor-cell-intrinsic GCH1 induced immunosuppression through metabolic reprogramming and IDO1 upregulation in TNBC. Inhibition of GCH1 by DAHP serves as a potential immunometabolic strategy in TNBC.

scholarly journals Sarcoma IL-12 overexpression facilitates NK cell immunomodulation

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mary Jo Rademacher ◽  
Anahi Cruz ◽  
Mary Faber ◽  
Robyn A. A. Oldham ◽  
Dandan Wang ◽  
...  
Keyword(s):  
Immune Response ◽  
Cell Lines ◽  
Nk Cell ◽  
Autologous Tumor ◽  
Murine Models ◽  
Lentiviral Transduction ◽  
Ifn Γ ◽  
Human Sarcoma

AbstractInterleukin-12 (IL-12) is an inflammatory cytokine that has demonstrated efficacy for cancer immunotherapy, but systemic administration has detrimental toxicities. Lentiviral transduction eliciting IL-12-producing human sarcoma for autologous reintroduction provides localized delivery for both innate and adaptive immune response augmentation. Sarcoma cell lines and primary human sarcoma samples were transduced with recombinant lentivirus engineering expression of human IL-12 (hu-IL-12). IL-12 expressing sarcomas were assessed in vitro and in vivo following implantation into humanized NSG and transgenic human IL-15 expressing (NSG.Tg(Hu-IL-15)) murine models. Lentiviral transduction (LV/hu-IL-12) of human osteosarcoma, Ewing sarcoma and rhabdomyosarcoma cell lines, as well as low-passage primary human sarcomas, engendered high-level expression of hu-IL-12. Hu-IL-12 demonstrated functional viability, eliciting specific NK cell-mediated interferon-γ (IFN-γ) release and cytotoxic growth restriction of spheroids in vitro. In orthotopic xenograft murine models, the LV/hu-IL-12 transduced human sarcoma produced detectable IL-12 and elicited an IFN-γ inflammatory immune response specific to mature human NK reconstitution in the NSG.Tg(Hu-IL-15) model while restricting tumor growth. We conclude that LV/hu-IL-12 transduction of sarcoma elicits a specific immune reaction and the humanized NSG.Tg(Hu-IL-15) xenograft, with mature human NK cells, can define in vivo anti-tumor effects and systemic toxicities. IL-12 immunomodulation through autologous tumor transduction and reintroduction merits exploration for sarcoma treatment.

scholarly journals Probiotic and Functional Properties of Limosilactobacillus reuteri INIA P572

Nutrients ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1860
Author(s):  
Patricia Diez-Echave ◽  
Izaskun Martín-Cabrejas ◽  
José Garrido-Mesa ◽  
Susana Langa ◽  
Teresa Vezza ◽  
...  
Keyword(s):  
In Vitro Assays ◽  
Immunomodulatory Activity ◽  
Probiotic Properties ◽  
Protective Effects ◽  
Mice Model ◽  
In Vivo Models ◽  
Food Borne ◽  
Gastrointestinal Conditions

Limosilactobacillus reuteri INIA P572 is a strain able to produce the antimicrobial compound reuterin in dairy products, exhibiting a protective effect against some food-borne pathogens. In this study, we investigated some probiotic properties of this strain such as resistance to gastrointestinal passage or to colonic conditions, reuterin production in a colonic environment, and immunomodulatory activity, using different in vitro and in vivo models. The results showed a high resistance of this strain to gastrointestinal conditions, as well as capacity to grow and produce reuterin in a human colonic model. Although the in vitro assays using the RAW 264.7 macrophage cell line did not demonstrate direct immunomodulatory properties, the in vivo assays using a Dextran Sulphate Sodium (DSS)-induced colitic mice model showed clear immunomodulatory and protective effects of this strain.

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