Adding a bio-response modifier and zinc oxide to piglet weaner diets influences immunological responses to weaning

The effect of zinc oxide (ZnO) and a Mycobacterium smegmatis-derived bio-response modifier (BRM) supplementation on blood neutrophil functions, high-mobility group box 1 (HMGB1) protein and pro-inflammatory cytokine responses was studied in early weanling piglets. In total, 45 piglets were placed in the following five groups: basal diet only (I), supplemented with ZnO (II), supplemented with BRM (III), supplemented with ZnO plus BRM (IV) in basal diet and basal diet without weaning from dam (V). The phagocytic activity, superoxide anion and myeloperoxidase production in blood neutrophils and the concentrations of HMGB1, TNF-α, IFN-γ and IL-1β in blood plasma were measured before and after weaning. The neutrophil functions were impaired and the concentrations of HMGB1, inflammatory cytokines, were elevated in piglets during the post-weaning period. The neutrophil functions were not improved until Day 7 of weaning (P > 0.05) and pronounced elevation (P < 0.05) in the concentration of pro-inflammatory cytokines and HMGB1 was observed until Days 14 and 21 respectively, in Groups II and III. The addition of BRM plus ZnO in basal diet improved superoxide anion and myeloperoxidase production on Day 2 (P < 0.05) and decreased the TNF-α and IFN-γ concentrations on Day 7 (P < 0.05), with no significant change in the level of IL-1β and HMGB1 in Group IV. Finally, it is concluded that addition of ZnO plus BRM in the diet induced the neutrophil functions and reduced the inflammatory cytokine response much earlier to stimulate innate immunity than did ZnO or BRM alone.

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Electron Ultra-High Dose Rate FLASH And Conventional Irradiation Induce Distinct Regulations of Inflammatory Cytokines And CD8 T Lymphocytes Ratio In Mice

10.21203/rs.3.rs-727597/v1 ◽

2021 ◽

Author(s):

De-Huan Xie ◽

Yi-Chuan Li ◽

Sai Ma ◽

Xin Yang ◽

Ruo-Ming Lan ◽

...

Keyword(s):

Flow Cytometry ◽

Dose Rate ◽

Inflammatory Cytokines ◽

Inflammatory Cytokine ◽

High Dose Rate ◽

Control Group ◽

High Dose ◽

Tnf Α ◽

Cytokine Levels ◽

Ifn Γ

Abstract Purpose: Ultra-high dose rate FLASH irradiation has been shown to cause less normal tissue damage compared with conventional irradiation, also termed “FLASH effect”. However, the underlying mechanism was scarcely known. The purpose of the present study was to determine whether FLASH and conventional irradiation would induce differential inflammatory cytokines expression. Materials and methods: Female FvB mice were randomly assigned to three different groups: non-irradiated control, conventional (CONV) and FLASH groups. Mice were irradiated at 6 to 19 Gy of CONV (0.1 Gy/s) or FLASH (38.5-600 Gy/s) irradiation using an Elekta Synergy linac (6 MeV). Mice were immobilized in prone position in a custom-designed applicator with dosimetry films positioned under the body. Dose were verified by Gafchromic films. Enzyme linked immunosorbent assay (ELISA) were performed in serum samples of the mice at 6, 18 and 31 days after irradiation for four inflammatory cytokines: tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin-6 (IL-6) and IL-10. Flow cytometry using antibodies for CD3, CD8, CD4 and CD45 in blood were performed pre- and 1-week post irradiation. Results: At D6 (18-19 Gy), both IL-6 and TNF-α were elevated, and IL-10 was reduced in FLASH and CONV group, while IFN-γ was only significantly increased in conventional group, compared with control group. At D18 (10 Gy) and D31 (13-19 Gy), conventional RT significantly elevated levels of IL-6, IFN-γ and TNF-α and reduced IL-10 level compared with FLASH group and control group. Additionally, even low dose conventional irradiation (13 Gy) could induce higher level of pro-inflammatory cytokines and lower level of anti-inflammatory cytokine than high dose (17-19 Gy) FLASH irradiation at D31. Flow cytometry showed that the CD8+/CD45+ ratio in the blood were higher in the conventional than in FLASH. These data indicate that minor inflammatory cytokine levels of serum in FLASH could be result of the absent of immune overactivation induced by conventional irradiation. Conclusions: Ultra-high dose rate electron FLASH caused less inflammatory cytokine levels of serum which might be a result from less CD8+/CD45+ ratio in the blood. Thus, differential cytokines and CD8+ T cell expression between FLASH and conventional irradiation would be a potential mechanism for “FLASH effect”.

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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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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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Inflammatory cytokines-stimulated human muscle stem cells ameliorate ulcerative colitis via the IDO-TSG6 axis

Stem Cell Research & Therapy ◽

10.1186/s13287-020-02118-3 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Shengchao Zhang ◽

Jiankai Fang ◽

Zhanhong Liu ◽

Pengbo Hou ◽

Lijuan Cao ◽

...

Keyword(s):

Ulcerative Colitis ◽

Stem Cells ◽

Mesenchymal Stem Cells ◽

Inflammatory Cytokines ◽

Human Muscle ◽

Enzyme Linked Immunosorbent Assay ◽

Muscle Stem Cells ◽

Tnf Α ◽

Ifn Γ ◽

Anti Inflammatory

Abstract Background Muscle stem cells (MuSCs) are absolutely required for the formation, repair, and regeneration of skeletal muscle tissue. Increasing evidence demonstrated that tissue stem cells, especially mesenchymal stem cells (MSCs), can exert therapeutic effects on various degenerative and inflammatory disorders based on their immunoregulatory properties. Human mesenchymal stem cells (hMSCs) treated with interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) were reported to possess anti-inflammatory functions by producing TNF-stimulated gene 6 (TSG-6). However, whether human muscle stem cells (hMuSCs) also possess TSG-6 mediated anti-inflammatory functions has not been explored. Methods The ulcerative colitis mouse model was established by subjecting mice to dextran sulfate sodium (DSS) in drinking water for 7 days. hMuSCs were pretreated with IFN-γ and TNF-α for 48 h and were then transplanted intravenously at day 2 of DSS administration. Body weights were monitored daily. Indoleamine 2,3-dioxygenase (IDO) and TSG-6 in hMuSCs were knocked down with short hairpin RNA (shRNA) and small interfering RNA (siRNA), respectively. Colon tissues were collected for length measurement and histopathological examination. The serum level of IL-6 in mice was measured by enzyme-linked immunosorbent assay (ELISA). Real-time PCR and Western blot analysis were performed to evaluate gene expression. Results hMuSCs treated with inflammatory factors significantly ameliorated inflammatory bowel disease (IBD) symptoms. IDO and TSG-6 were greatly upregulated and required for the beneficial effects of hMuSCs on IBD. Mechanistically, the tryptophan metabolites, kynurenine (KYN) or kynurenic acid (KYNA) produced by IDO, augmented the expression of TSG-6 through activating their common receptor aryl hydrocarbon receptor (AHR). Conclusion Inflammatory cytokines-treated hMuSCs can alleviate DSS-induced colitis through IDO-mediated TSG-6 production.

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Human Herpesvirus 6A Induces Dendritic Cell Death and HMGB1 Release without Virus Replication

Pathogens ◽

10.3390/pathogens10010057 ◽

2021 ◽

Vol 10 (1) ◽

pp. 57

Author(s):

Rasmus Gustafsson

Keyword(s):

Cell Death ◽

Dendritic Cells ◽

High Mobility ◽

Human Herpesvirus ◽

Human Monocyte ◽

Hmgb1 Protein ◽

Innate And Adaptive Immunity ◽

Th2 Polarization ◽

Dependent Cell ◽

Ifn Γ

Human herpesvirus 6A (HHV-6A) is a common virus that has important immunomodulatory effects. Dendritic cells (DC) are key players in innate and adaptive immunity and are implicated in the pathogenesis of many human diseases, including infections. (1) Background: Previous studies have demonstrated suppressive effects of HHV-6A on key DC functions. (2) Methods: human monocyte derived dendritic cells were inoculated with HHV-6A and viral replication, cell viability, and release of high mobility group box 1 (HMGB1) protein from DC and of the cytokines IL-2, IL-4, IL-6, IL-10, TNF and IFN-γ after co-culture with allogenic CD4+ T cells were assessed. (3) Results: Nonproductive infection of HHV-6A in DC leads to titer-dependent cell death and the release of HMGB1 protein, and a Th2 polarization. (4) Conclusion: These immune responses aimed to clear the infection may also imply risks for inflammatory pathologies associated with HHV-6A such as multiple sclerosis.

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SLAMF7 engagement super-activates macrophages in acute and chronic inflammation

10.1101/2020.11.05.368647 ◽

2020 ◽

Author(s):

Daimon P. Simmons ◽

Hung N. Nguyen ◽

Emma Gomez-Rivas ◽

Yunju Jeong ◽

Antonia F. Chen ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Immune Responses ◽

Inflammatory Cytokine ◽

Macrophage Activation ◽

Rna Seq ◽

Autocrine Signaling ◽

Tnf Α ◽

Activated Macrophage ◽

Ifn Γ ◽

Acute And Chronic Inflammation

AbstractMacrophages regulate protective immune responses to infectious microbes, but aberrant macrophage activation frequently drives pathological inflammation. To identify regulators of vigorous macrophage activation, we analyzed RNA-seq data from synovial macrophages and identified SLAMF7 as a receptor associated with a super-activated macrophage state in rheumatoid arthritis. We implicated IFN-γ as a key regulator of SLAMF7 expression. Engaging this receptor drove an exuberant wave of inflammatory cytokine expression, and induction of TNF-α following SLAMF7 engagement amplified inflammation through an autocrine signaling loop. We observed SLAMF7-induced gene programs not only in macrophages from rheumatoid arthritis patients, but in gut macrophages from active Crohn’s disease patients and lung macrophages from severe COVID-19 patients. This suggests a central role for SLAMF7 in macrophage super-activation with broad implications in pathology.

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P0527AROLE OF PROMOTING INFLAMMATION OF KLF6 IN ACUTE KIDNEY INURY

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p0527a ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Dan Li ◽

Chenyu Li ◽

Yan Xu

Keyword(s):

Inflammatory Cytokines ◽

Inflammatory Cytokine ◽

Ischemia Reperfusion ◽

Kidney Injury ◽

Tnf Α ◽

Public Dataset ◽

Anti Inflammatory ◽

Anti Inflammatory Cytokine ◽

Pro Inflammatory Cytokines

Abstract Background and Aims Acute kidney injury (AKI), commonly appeared in cardiac arrest, surgery and kidney transplantation which involved in ischemia-reperfusion (IR) injury of kidney. However, the mechanisms underlying inflammatory response in IR AKI is still unclear. Method Public dataset showed kruppel-like factor 6 (KLF6) was significantly highly expressed (P<0.05) in AKI, implies KLF6 might be associated with AKI. To evaluate the mechanism of KLF6 on IR AKI, 30 rats were randomly divided into sham and IR group, and were sacrificed at 0 h, 3 h, 6 h, 12 h or 24 h after IR. Results The results showed KLF6 expression was peaking at 6 h after IR, and the expression of pro-inflammatory cytokines MCP-1 and TNF-α were increased both in serum and kidney tissues after IR, while anti-inflammatory cytokine IL-10 was decreased after IR. Furthermore, in vitro results showed KLF6 knock-down reduced the pro-inflammatory cytokines expression and increased the anti-inflammatory cytokines expression. Conclusion These results suggest that (1) KLF6 might be a novel biomarker for early diagnosis of AKI and (2) targeting KLF6 expression may offer novel strategies to protect kidneys from IR AKI Figure KLF6, AKI, Control Inflammation

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Priming effects of GM-CSF, IFN-γ and TNF-α on human neutrophil inflammatory cytokine production

Melanoma Research ◽

10.1097/00008390-200204000-00004 ◽

2002 ◽

Vol 12 (2) ◽

pp. 123-128 ◽

Cited By ~ 22

Author(s):

E. Jabuulońska ◽

M. Kiluk ◽

W. Markiewicz ◽

J. Jabuuloński

Keyword(s):

Human Neutrophil ◽

Inflammatory Cytokine ◽

Cytokine Production ◽

Priming Effects ◽

Inflammatory Cytokine Production ◽

Gm Csf ◽

Tnf Α ◽

Ifn Γ

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Comparison of Concanavalin a-Induced Murine Autoimmune Hepatitis Models

Cellular Physiology and Biochemistry ◽

10.1159/000489074 ◽

2018 ◽

Vol 46 (3) ◽

pp. 1241-1251 ◽

Cited By ~ 19

Author(s):

Tinghong Ye ◽

Tingting Wang ◽

Xiaoxue Yang ◽

Xiaoli Fan ◽

Maoyao Wen ◽

...

Keyword(s):

Autoimmune Hepatitis ◽

Inflammatory Cytokines ◽

Concanavalin A ◽

Current Treatment ◽

Human Condition ◽

Type I ◽

Therapeutic Approaches ◽

Tnf Α ◽

Ifn Γ ◽

New Treatments

Background/Aims: Autoimmune hepatitis (AIH) is a chronic necroinflammatory disease of the liver whose pathogenic mechanisms have not yet been elucidated. Moreover, the current treatment used for the vast majority of AIH patients is largely dependent on immunosuppressant administration and liver transplantation. However, research on the pathogenesis of AIH and effective new treatments for AIH have been hampered by a lack of animal models that accurately reproduce the human condition. Methods: AIH models created by concanavalin A (ConA) injections at different times and doses. The levels of ALT, AST, LDH and inflammatory cytokines were examined at various times after 20 mg/kg ConA was administered by ELISA using commercially available kits. Moreover, liver pathological changes were observed by flow cytometry (FCM) and H&E staining. Results: Our experiments demonstrated that the levels of ALT, AST, LDH and several inflammatory cytokines, including TNF-α, IFN-γ, and IL-6, were higher in the 20 mg/kg 12 h ConA group than in the other groups. Importantly, the numbers of activated CD4+ and CD8+ T lymphocytes in the blood, spleen and liver were calculated. These results showed that ConA (20 mg/kg for 12 h)-induced hepatitis was similar to that in clinical AIH patients. Furthermore, we found that the number of MDSCs in the blood was significantly increased in the ConA (20 mg/kg for 12 h) group compared with controls. Our findings indicated that ConA (20 mg/kg for 12 h)-induced hepatitis could be used as an experimental murine model that mirrors most of the pathogenic properties of human type I AIH. Conclusion: This model [ConA (20 mg/kg for 12 h)] provides a valuable tool for studying AIH immunopathogenesis and rapidly assessing novel therapeutic approaches.

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