Effect of interferon-γ treatment on the expression of interleukin-1β at the maternal - fetal interface of pregnant rats

2007 ◽  
Vol 19 (3) ◽  
pp. 510 ◽  
Author(s):  
Hong-Fei Xia ◽  
Quan-Hong Sun ◽  
Jing-Pian Peng
Keyword(s):  
Late Pregnancy ◽  
Interferon Γ ◽  
Control Group ◽  
Cytokine Network ◽  
Pregnant Rats ◽  
Endometrial Stromal Cells ◽  
Protein Levels ◽  
Decidua Basalis ◽  
Ifn Γ

In the present study, the possible mechanisms by which interferon (IFN)-γ affects pregnancy were investigated using the cytokine network model. The IFN-γ-induced expression of interleukin (IL)-1β was examined using western blotting, immunohistochemistry and immunofluorescence. The results showed that IFN-γ treatment significantly decreased the expression of uterine IL-1β protein during the preimplantation, post-implantation and mid-gestation periods. The expression of IL-1β protein was increased after IFN-γ treatment compared with the control group in late pregnancy. In the placenta, IL-1β protein levels were significantly increased after IFN-γ treatment in early and mid-pregnancy. In late pregnancy, IFN-γ treatment significantly decreased placental IL-1β protein levels. IL-1β was mainly expressed in the myometrium, uterine arteries, decidua basalis, trophospongium of the junctional layer and trophoblastic epithelium of the labyrinthine layers. IL-1β was mainly located in the cytoplasm of in vitro cultured endometrial stromal cells (ESCs). IFN-γ treatment did not affect the distribution of IL-1β, only the expression of IL-1β. The effects of IFN-γ on the proliferation of ESCs were determined using an MTS (a novel tetrazolium compound) assay. IFN-γ treatment inhibited the proliferation of ESCs and decreased the weight of the fetus and placenta. These results indicate that exogenous IFN-γ affects the expression of IL-1β and inhibits ESC proliferation.

scholarly journals Assessment of Cytotoxicity, Fetotoxicity, and Teratogenicity ofPlathymenia reticulataBenth Barks Aqueous Extract

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Lia de Barros Leite Albuquerque ◽  
Cháriston André Dal Belo ◽  
Marcio Galdino dos Santos ◽  
Patricia Santos Lopes ◽  
Marli Gerenutti ◽  
...  
Keyword(s):  
Aqueous Extract ◽  
Reproductive Toxicity ◽  
Late Pregnancy ◽  
Control Group ◽  
Corpora Lutea ◽  
Experimental Conditions ◽  
Pregnant Rats ◽  
Skeletal Analysis ◽  
Ld50 Test

Scientific assessment of harmful interactions of chemicals over the entire reproductive cycle are divided into three segments based on the period: from premating and mating to implantation (I), from implantation to major organogenesis (II), and late pregnancy and postnatal development (III). We combined the segments I and II to assessPlathymenia reticulataaqueous extract safety. In order to investigate reproductive toxicity (segment I), pregnant rats received orally 0.5 or 1.0 g/kg of extract, daily, during 18 days. These concentrations were determined by a preliminaryin vitroLD50 test in CHO-k1 cells. A control group received deionized water. The offspring was removed at the 19th day, by caesarean, and a teratology study (segment II) was carried out. The corpora lutea, implants, resorptions, live, and dead fetuses were then counted. Placenta and fetuses were weighted. External and visceral morphology were provided by the fixation of fetuses in Bouin, whereas skeletal analysis was carried out on the diaphanizated ones. The increase in the weights of placenta and fetuses was the only abnormality observed. Since there was no sign of alteration on reproduction parameters at our experimental conditions, we conclude thatP. reticulataaqueous extract is safe at 0.5 to 1.0 g/kg and is not considered teratogenic.

In Vitro and In Vivo Evidence That the PP2A Inhibitor SET Regulates IFN-γ Production in Monokine-Stimulated Natural Killer Cells.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 928-928 ◽  
Author(s):  
Rossana Trotta ◽  
Jessica Dal Col ◽  
Jeffrey Allard ◽  
Paolo Neviani ◽  
Ramasamy Santhanam ◽  
...  
Keyword(s):  
Nk Cells ◽  
Natural Killer ◽  
Interferon Γ ◽  
Oligonucleotide Array ◽  
Pp2a Activity ◽  
Protein Levels ◽  
Ifn Γ ◽  
Protein Phosphatase Type

Abstract Monokines (i.e. IL-12, IL-18 and IL-15) induce natural killer (NK) cells to produce interferon-γ (IFN-γ), which is critical for monocyte clearance of infectious pathogens and tumor surveillance. To identify new regulators of IFN-γ production we performed oligonucleotide array analysis of unstimulated and IL-12- and IL-18-stimulated NK92 cells. Among the subset of mRNAs differentially regulated in monokine-stimulated cells, we found SET, a potent inhibitor of the protein phosphatase type 2A (PP2A). SET mRNA and/or protein levels were upregulated in IL-12/IL-18- and IL-12/IL-15-stimulated primary human NK cells. Interestingly, the SET protein is also selectively increased in the resting CD56bright NK subset, which is a potent producer of IFN-γ relative to the CD56dim NK subset. To determine whether SET positively regulates IFN-γ production by inhibiting PP2A activity, we employed RNAi and interfered with SET expression in NK92 cells. SET downregulation inhibited IFN-γ secretion by IL-12/IL-18, IL-12/IL-15- or IL-15/IL-18-stimulated NK92 cells. By contrast, ectopic SET expression increased IFN-γ production in monokine-stimulated NK92 and primary human NK cells. Because downregulation of SET augmented PP2A activity in NK92 cells, we sought to investigate whether pharmacologic activation of PP2A inhibits the ability of NK cells to produce IFN-γ. Indeed, suppression of IFN-γ expression and secretion was also observed upon treatment of NK92 and primary NK cells with 1,9-dideoxy-forskolin, a known inducer of PP2A activity. Accordingly, NK cells from mice treated with 1.9-dideoxy-forskolin produced less IFN-γ in response to in vivo monokine stimulation than did NK cells from vehicle-treated mice. Mechanistically, activation of PP2A by SET knock-down or 1,9-dideoxy-forskolin treatment leads to inhibition of ERK1/2, p65RelA and STAT5 activity in monokine-stimulated NK cells. Because these signaling molecules are important for IFN-γ production by monokine-stimulated NK cells, our results strongly suggest that monokine induction of SET expression in NK cells is essential for limiting PP2A activity that, otherwise, would negatively impact the ability of NK cells to produce and release optimal levels of IFN-γ.

scholarly journals The Role of Interleukine-10 and Interferon-γ as Potential Markers of the Evolution of African Swine Fever Virus Infection in Wild Boar

Pathogens ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 757
Author(s):  
Sandra Barroso-Arévalo ◽  
Jose A. Barasona ◽  
Estefanía Cadenas-Fernández ◽  
José M. Sánchez-Vizcaíno
Keyword(s):  
Wild Boar ◽  
Vaccine Candidate ◽  
African Swine Fever Virus ◽  
African Swine Fever ◽  
Interferon Γ ◽  
Fever Virus ◽  
Control Group ◽  
Challenge Virus ◽  
Ifn Γ

African swine fever virus (ASFv) is one of the most challenging pathogens to affect both domestic and wild pigs. The disease has now spread to Europe and Asia, causing great damage to the pig industry. Although no commercial vaccine with which to control the disease is, as yet, available, some potential vaccine candidates have shown good results in terms of protection. However, little is known about the host immune mechanisms underlying that protection, especially in wild boar, which is the main reservoir of the disease in Europe. Here, we study the role played by two cytokines (IL-10 and IFN-γ) in wild boar orally inoculated with the attenuated vaccine candidate Lv17/WB/Rie1 and challenged with a virulent ASFv genotype II isolate. A group of naïve wild boar challenged with the latter isolate was also established as a control group. Our results showed that both cytokines play a key role in protecting the host against the challenge virus. While high levels of IL-10 in serum may trigger an immune system malfunctioning in challenged animals, the provision of stable levels of this cytokine over time may help to control the disease. This, together with high and timely induction of IFN-γ by the vaccine candidate, could help protect animals from fatal outcomes. Further studies should be conducted in order to support these preliminary results and confirm the role of these two cytokines as potential markers of the evolution of ASFV infection.

YAP1 Overexpression Is Associated with Kidney Dysfunction in Lupus Nephritis

Pathobiology ◽  
2021 ◽  
pp. 1-12
Author(s):  
Ying Xie ◽  
Yuanyuan Ruan ◽  
Huimei Zou ◽  
Yixin Wang ◽  
Xin Wu ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Epithelial Mesenchymal Transition ◽  
Kidney Tissue ◽  
Mouse Kidney ◽  
Experimental Comparison ◽  
Control Group ◽  
Mrna Levels ◽  
Mesenchymal Transition ◽  
Protein Levels

<b><i>Objective:</i></b> The goal of the present study was to determine the expression of yes-associated protein 1 (YAP1) in renal tissues of mice with lupus nephritis (LN) and elucidate its role in the progression of renal fibrosis. <b><i>Methods:</i></b> C57BL/6 mice and MRL/lpr mice were selected for experimental comparison. Mouse kidney tissues were removed and sectioned for hematoxylin and eosin staining, Masson’s trichome staining, Sirius staining, and immunohistochemistry. The mRNA and protein levels of YAP1 in mouse kidney tissues were detected, and the correlation between YAP1 and fibronectin (FN) mRNA levels was analyzed. Mouse renal epithelial cells were used for in vitro experiments. After transfection and stimulation, the cells were divided into 4 groups, namely the C57BL/6 serum group (group 1), the MRL/lpr serum group (group 2), the MRL/lpr serum + siRNA-negative control group (group 3), and the MRL/lpr serum + siRNA-YAP1 group (group 4). Epithelial-mesenchymal transition (EMT) markers in each group were detected by Western blotting and immunofluorescence staining. Serum creatinine, blood urea nitrogen, and urinary protein levels were detected and assessed for their correlation with YAP1 mRNA levels by Spearman’s analysis. <b><i>Results:</i></b> Compared to C57BL/6 mice, MRL/lpr mice exhibited obvious changes in fibrosis in renal tissues. In addition, YAP1 expression was significantly higher in the renal tissues of MRL/lpr mice than in those of C57BL/6 mice, and YAP1 mRNA levels were positively correlated with those of FN. YAP1 silencing in lupus serum-stimulated cells could effectively relieve serum-induced EMT. Finally, we observed that YAP1 mRNA levels in mouse kidney tissue were significantly and positively correlated with the degree of renal function injury. <b><i>Conclusion:</i></b> YAP1 expression in the kidney tissues of LN mice was higher than that observed in normal mice, indicating that YAP1 may play an important role in the occurrence and development of LN.

A Summary of the Third Global Interferon-γ Release Assay Symposium

2013 ◽  
Vol 34 (6) ◽  
pp. 619-624 ◽  
Author(s):  
Antonino Catanzaro ◽  
Charles Daley
Keyword(s):  
Immune Response ◽  
Tuberculin Skin Test ◽  
Skin Test ◽  
Interferon Γ ◽  
Enzyme Linked Immunosorbent Assay ◽  
In Vitro Tests ◽  
The Third ◽  
Specific Antigens ◽  
Ifn Γ

Studies over the past several decades have dramatically increased our understanding of the immune response to Mycobacterium tuberculosis infection, and advances in proteomics and genomics have led to a new class of immune-diagnostic tests, termed interferon-γ (IFN-γ) release assays (IGRAs), which appear to obviate many of the problems encountered with the tuberculin skin test (TST). Worldwide, 2 IGRAs are currently commercially available. QuantiFERON-TB Gold In-Tube (Cellestis) is a third-generation product that uses an enzyme-linked immunosorbent assay to measure IFN-γ generated in whole blood stimulated with M. tuberculosis–specific antigens. T-Spot-TB (Oxford Immunotec) employs enzyme-linked immunosorbent spot technology to enumerate the number of purified lymphocytes that respond to M. tuberculosis–specific antigens by producing IFN-γ. These in vitro tests measure the host immune response to M. tuberculosis–specific antigens, which virtually eliminates false-positive cross reactions caused by bacillus Calmette-Guérin vaccination and/or exposure to environmental nontuberculous mycobacteria that plague the interpretation and accuracy of the tuberculin skin test (TST). The high specificity of IGRAs, together with sensitivity commensurate with or better than that of the TST, promises an accurate diagnosis and the ability to focus tuberculosis-control activities on those who are actually infected with M. tuberculosis. The Third Global Symposium was held over a 3-day period and was presented by the University of California, San Diego, Continuing Medical Education department; slides and sound recordings of each presentation are available at http://cme.ucsd.edu/igras/syllabus.html. A moderated discussion is also available at http://cme.ucsd.edu/igrasvideo. This document provides a summary of the key findings of the meeting, specifically focusing on the use of IGRAs in screening healthcare worker populations.

scholarly journals The Role of the FOXO1/β2-AR/p-NF-κB p65 Pathway in the Development of Endometrial Stromal Cells in Pregnant Mice under Restraint Stress

2021 ◽  
Vol 22 (3) ◽  
pp. 1478
Author(s):  
Jiayin Lu ◽  
Yaoxing Chen ◽  
Zixu Wang ◽  
Jing Cao ◽  
Yulan Dong
Keyword(s):  
Oxidative Stress ◽  
Stromal Cells ◽  
Restraint Stress ◽  
Target Genes ◽  
Mrna Levels ◽  
Endometrial Stromal Cells ◽  
Protein Levels ◽  
Pregnant Mice

Restraint stress causes various maternal diseases during pregnancy. β2-Adrenergic receptor (β2-AR) and Forkhead transcription factor class O 1 (FOXO1) are critical factors not only in stress, but also in reproduction. However, the role of FOXO1 in restraint stress, causing changes in the β2-AR pathway in pregnant mice, has been unclear. The aim of this research was to investigate the β2-AR pathway of restraint stress and its impact on the oxidative stress of the maternal uterus. In the study, maternal mice were treated with restraint stress by being restrained in a transparent and ventilated device before sacrifice on Pregnancy Day 5 (P5), Pregnancy Day 10 (P10), Pregnancy Day 15 (P15), and Pregnancy Day 20 (P20) as well as on Non-Pregnancy Day 5 (NP5). Restraint stress augmented blood corticosterone (CORT), norepinephrine (NE), and blood glucose levels, while oestradiol (E2) levels decreased. Moreover, restraint stress increased the mRNA levels of the FOXO family, β2-AR, and even the protein levels of FOXO1 and β2-AR in the uterus and ovaries. Furthermore, restraint stress increased uterine oxidative stress level. In vitro, the protein levels of FOXO1 were also obviously increased when β2-AR was activated in endometrial stromal cells (ESCs). In addition, phosphorylated-nuclear factor kappa-B p65 (p-NF-κB p65) and its target genes decreased significantly when FOXO1 was inhibited. Overall, it can be said that the β2-AR/FOXO1/p-NF-κB p65 pathway was activated when pregnant mice were under restraint stress. This study provides a scientific basis for the origin of psychological stress in pregnant women.

scholarly journals Effect ofTityus serrulatusvenom on cytokine production and the activity of murine macrophages

2002 ◽  
Vol 11 (1) ◽  
pp. 23-31 ◽  
Author(s):  
Vera L. Petricevich
Keyword(s):  
Cytokine Production ◽  
Peritoneal Macrophages ◽  
Interferon Γ ◽  
Enzyme Linked Immunosorbent Assay ◽  
No Production ◽  
Dependent Manner ◽  
Immune Functions ◽  
Macrophage Activity ◽  
Ifn Γ

The purpose of this study was to investigate the effects ofTityus serrulatusvenom (TSV) on murine peritoneal macrophages evaluated in terms of activation. The effects of crude TSV were analysed by detection of cytokines, oxygen intermediate metabolites (H2O2) and nitric oxide (NO) in supernatants of peritoneal macrophages. Several functional bioassays were employed including anin vitromodel for envenomating: cytotoxicity of TSV was assessed using the lyses percentage. Tumor necrosis factor (TNF) activity was assayed by measuring its cytotoxic activity on L-929 cells, and interleukin-6 (IL-6) and interferon-γ (IFN-γ) were assayed by enzyme-linked immunosorbent assay, whereas NO levels were detected by Griess colorimetric reactions in culture supernatant of macrophages incubated with TSV and subsequently exposed to either lipopolysaccharide or IFN-γ. Incubation of macrophages with TSV increased production of IL-6 and IFN-γ in a dose-dependent manner. TNF production was not detected in supernatants treated with TSV at any concentration. The increase in IL-6 secretion was not associated with concentration-dependent cytoxicity of TSV on these cells. These data suggest that the cytotoxicity does not appear to be the main cause of an increased cytokine production by these cells. Although NO is an important effector molecule in macrophage microbicidal activity, the inducing potential of the test compounds for its release was found to be very moderate, ranging from 125 to 800 mM. Interestingly, NO levels of peritoneal macrophages were increased after IFN-γ. Moreover, NO production had an apparent effect on macrophage activity. The results obtained here also shown that the TSV induces an important elevation in H2O2release. These results combined with NO production suggest that TSV possesses significant immunomodulatory activities capable of stimulating immune functionsin vitro.

scholarly journals Siraitia grosvenorii Residual Extract Attenuates Atopic Dermatitis by Regulating Immune Dysfunction and Skin Barrier Abnormality

Nutrients ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3638
Author(s):  
Yoon-Young Sung ◽  
Heung-Joo Yuk ◽  
Won-Kyung Yang ◽  
Seung-Hyung Kim ◽  
Dong-Seon Kim
Keyword(s):  
Atopic Dermatitis ◽  
Immunoglobulin E ◽  
Allergic Inflammation ◽  
Skin Barrier ◽  
Human Keratinocytes ◽  
Skin Lesions ◽  
Protein Levels ◽  
Siraitia Grosvenorii ◽  
Ifn Γ

Atopic dermatitis is a persistent inflammatory skin disorder. Siraitia grosvenorii fruits (monk fruit or nahangwa in Korean, NHG) are used as a natural sweetener and as a traditional medicine for the treatment of asthma and bronchitis. We evaluated the activity of S. grosvenorii residual extract (NHGR) on allergic inflammation of atopic dermatitis in a Dermatophagoides farinae mite antigen extract (DfE)-treated NC/Nga murine model and in vitro. Oral administration of NHGR significantly reduced epidermal hyperplasia and inflammatory cell infiltration in the skin lesions of DfE-induced atopic dermatitis, as well as the dermatitis severity score. NHGR reduced serum immunoglobulin E levels. Splenic concentrations of IFN-γ, interleukin (IL)-4, IL-5, and IL-13 were reduced by NHGR administration. Immunohistofluorescence staining showed that NHGR administration increased the protein levels of claudin-1, SIRT1, and filaggrin in atopic dermatitis skin lesions. In addition, NHGR inhibited the phosphorylation of mitogen-activated protein kinases and decreased filaggrin and chemokine protein expression in TNF-α/IFN-γ-induced human keratinocytes. Moreover, NHGR also inhibited histamine in mast cells. The quantitative analysis of NHGR revealed the presence of grosvenorine, kaempferitrin, and mogrosides. These results demonstrate that NHGR may be an efficient therapeutic agent for the treatment of atopic dermatitis.

scholarly journals Hemodialysis-Related Lymphomononuclear Release of Interleukin-12 in Patients with End-Stage Renal Disease

1999 ◽  
Vol 10 (10) ◽  
pp. 2171-2176 ◽  
Author(s):  
BRUNO MEMOLI ◽  
LUIGI MARZANO ◽  
VINCENZO BISESTI ◽  
MICHELE ANDREUCCI ◽  
BRUNA GUIDA
Keyword(s):  
Mononuclear Cells ◽  
Interferon Γ ◽  
Interleukin 12 ◽  
Control Group ◽  
Peripheral Blood Mononuclear ◽  
Mitogen Stimulation ◽  
Ifn Γ ◽  
Uremic Patients ◽  
Stage Renal Disease ◽  
End Stage

Abstract. Interleukin-12 (IL-12) is a cytokine produced by peripheral blood mononuclear cells (PBMC) that causes interferon-γ (IFN-γ) production and enhancement of cell-mediated cytotoxicity. To clarify the role of hemodialysis biocompatibility on IL-12 production and uremic immunodeficiency, we have studied the IL-12 and IFN-γ release by PBMC harvested from 12 patients dialyzed with cuprophan membrane (CU), eight patients dialyzed with polymethylmethacrylate membrane (PMMA), and eight nondialyzed uremic patients (UR). Ten healthy subjects constituted the control group (CON). PBMC were cultured for 48 h with and without nonspecific mitogen stimulation. In unstimulated conditions, CU showed an IL-12 PBMC production higher than CON, UR, and PMMA (46.67 ± 30.13versus2.56 ± 1.38, 6.16 ± 7.09, and 4.62 ± 4.76 pg/ml, respectively;P< 0.01). IL-12 production was correlated with C3a concentration measured at the outlet of hemodialyzer after 15 min of dialysis (r= 0.69,P< 0.01). IL-12 release in CU remained unchanged under mitogen stimulation (44.34 ± 23.86 pg/ml) and was lower than in CON, UR, and PMMA (66.0 ± 12.41, 68.37 ± 25.78, and 67.75 ± 22.61 pg/ml, respectively;P< 0.05). IFN-γ production was similar, in unstimulated conditions, in all groups. Under stimulation, IFN-γ release was lower in CU (13.42 ± 12.04 IU/ml) than in CON, UR, and PMMA (51.84 ± 30.74, 32.16 ± 13.86, and 32.16 ± 13.86 IU/ml, respectively;P< 0.01). These results demonstrate that hemodialysis with CU induces monocyte activation with an enhanced release of IL-12. On the contrary, stimulated PBMC production of both IL-12 and IFN-γ is lower in these patients than in CON, UR, and PMMA. The altered release of these cytokines could play a role in cell-mediated immunodeficiency of the uremic patients dialyzed with CU.

scholarly journals Glutamine modifies immune responses of mice infected with porcine circovirus type 2

2013 ◽  
Vol 110 (6) ◽  
pp. 1053-1060 ◽  
Author(s):  
Wenkai Ren ◽  
Yinghui Li ◽  
Xinglong Yu ◽  
Wei Luo ◽  
Gang Liu ◽  
...  
Keyword(s):  
Experimental Period ◽  
Porcine Circovirus Type ◽  
Virus Genome ◽  
Porcine Circovirus Type 2 ◽  
Porcine Circovirus ◽  
Glutamine Supplementation ◽  
Control Group ◽  
Protein Levels ◽  
Ifn Γ

The present study was conducted to evaluate the immune-enhancing effects of dietaryl-glutamine supplementation in porcine circovirus type 2 (PCV2)-infected mice, and to examine the clearance effects of glutamine against PCV2 in experimentally infected mice. A total of sixty Kunming female mice were infected with PCV2 at a dose of 100 TCID50(50 % tissue culture infection dose) by intraperitoneal injection after 2 weeks of dietaryl-glutamine supplementation orl-alanine supplementation (as the control (isonitrogenous) group). The measured variables on 3rd, 5th, 7th, 9th and 11th d post-infection (dpi) included: (1) PCV2 virus loaded in the liver, spleen, heart, lung, kidney, ovary and serum was determined by real-time PCR; (2) IL-2, IL-6, IL-10, interferon (IFN)-α, IFN-γ and C-reactive protein levels in serum were measured by ELISA; (3) serum total superoxide dismutase activity was measured spectrophotometrically at 550 nm absorbance. Dietaryl-glutamine supplementation significantly increased serum IL-2 levels on the 3rd (P< 0·01), 5th (P< 0·01), 7th (P< 0·05) and 9th dpi, significantly (P< 0·05) increased serum IL-6 levels on 3rd dpi, significantly (P< 0·05) increased serum IFN-γ levels on the 9th and 11th dpi and significantly decreased (P< 0·01) serum IL-10 levels on the 9th and 11th dpi, compared with those in the control group. Meanwhile, the PCV2 virus genome was detected sporadically throughout the experimental period in both groups. Taken together, the present results suggest that dietaryl-glutamine supplementation enhances immune function in PCV2-infected mice.

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