scholarly journals Interleukin-10 inhibits the in vivo and in vitro adverse effects of TNF-α on the endothelium of murine aorta

2010 ◽  
Vol 299 (4) ◽  
pp. H1160-H1167 ◽  
Author(s):  
Saiprasad M. Zemse ◽  
Chin Wei Chiao ◽  
Rob H. P. Hilgers ◽  
R. Clinton Webb
Keyword(s):  
Endothelial Dysfunction ◽  
Interleukin 10 ◽  
Enos Expression ◽  
Response Curves ◽  
Female Mice ◽  
In Vivo Experiments ◽  
Tnf Α ◽  
Significant Impairment

TNF-α is a proinflammatory cytokine and is an important mediator of maternal endothelial dysfunction leading to preeclampsia. In this study, we tested whether IL-10 protects against TNF-α-induced endothelial dysfunction in murine aorta. In in vitro experiments, aortic rings of C57BL/6 female mice were incubated in Dulbecco's modified Eagle's medium in the presence of either vehicle (distilled H2O), TNF-α (4 nmol/l), or recombinant mouse IL-10 (300 ng/ml) or in the presence of both TNF-α and IL-10 for 22 h at 37°C. In in vivo experiments C57BL6/IL-10 knockout female mice were treated with saline or TNF-α (220 ng·kg−1·day−1) for 14 days. Aortic rings were isolated from in vitro and in vivo experiments and mounted in a wire myograph (Danish Myotech) and stretched to a tension of 5 mN. Endothelium-dependent relaxation was assessed by constructing cumulative concentration-response curves to acetylcholine (ACh, 0.001–10 μmol/l) during phenylephrine (10 μmol/l)-induced contraction. As a result, overnight exposure of aortic rings to TNF-α resulted in significant blunted maximal relaxing responses ( Emax) to ACh compared with untreated rings (22 ± 4 vs. 82 ± 3%, respectively). IL-10 knockout mice treated with TNF-α showed significant impairment in ACh responses ( Emax) compared with C57BL/6 mice treated with TNF-α (51 ± 3 vs. 72 ± 3%, respectively). Western blot analysis showed that endothelial nitric oxide synthase (eNOS) expression was reduced by TNF-α in in vitro and in vivo experiments, whereas IL-10 restored the eNOS expression. In conclusion, the anti-inflammatory cytokine IL-10 prevents impairment in endothelium-dependent vasorelaxation caused by TNF-α by protecting eNOS expression.

scholarly journals Steroid Sulfates from Ophiuroids (Brittle Stars): Action on Some Factors of Innate and Adaptive Immunity

2016 ◽  
Vol 11 (6) ◽  
pp. 1934578X1601100
Author(s):  
Anna K Gazha ◽  
Lyudmila A. Ivanushko ◽  
Eleonora V. Levina ◽  
Sergey N. Fedorov ◽  
Tatyana S. Zaporozets ◽  
...  
Keyword(s):  
Adaptive Immunity ◽  
Inflammatory Cytokines ◽  
Brittle Stars ◽  
Innate And Adaptive Immunity ◽  
Functional Activities ◽  
In Vivo Experiments ◽  
Tnf Α ◽  
Pro Inflammatory Cytokines

The action of seven polyhydroxylated sterol mono- and disulfates (1-7), isolated from ophiuroids, on innate and adaptive immunity was examined in in vitro and in vivo experiments. At least, three of them (1, 2 and 4) increased the functional activities of neutrophils, including levels of oxygen-dependent metabolism, adhesive and phagocytic properties, and induced the expression of pro-inflammatory cytokines TNF-α and IL-8. Compound 4 was the most active for enhancing the production of antibody forming cells in the mouse spleen.

scholarly journals Elevated Expression of lncRNA MEG3 Induces Endothelial Dysfunction on HUVECs of IVF Born Offspring via Epigenetic Regulation

2020 ◽  
Author(s):  
Ying Jiang ◽  
Hong Zhu ◽  
Hong Chen ◽  
Meng-Meng Yang ◽  
Yi-Chen Yu ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Umbilical Vein ◽  
Methylation Status ◽  
Vitro Fertilization ◽  
In Vivo Experiments ◽  
Elevated Expression ◽  
Nitrite Nitrate ◽  
Umbilical Vein Endothelial Cells

Abstract Background: The cardiovascular dysfunction in children born after in vitro fertilization (IVF) has been of great concern, in our study, we aim to explore potential molecular mechanism for such long-term outcomes. Methods：Real-time qPCR was used to test long non-coding RNA MEG3 and endothelium-derived factors, endothelial nitric oxide synthase (eNOS), endothelin-1(ET1), vascular endothelial growth factor (VEGF). Primary HUVEC after caesarean section was treated with different estradiol concentrations in vitro. Besides, knockdown of MEG3 on HUVEC provided further evidence between MEG3 expression and alteration of NO, ET1, VEGF. Then, by using pyrosequencing, we detected MEG3 promoter methylation status.Results: We found that the expression level of MEG3 was higher in human umbilical vein endothelial cells (HUVECs) of IVF offspring than that in spontaneously born offspring. Furthermore, we found decreased expression of eNOS, VEGF, elevated expression of ET1 in HUVECs from IVF offspring compared to spontaneously born offspring. We further confirmed the results from in-vivo experiments by demonstrating that high-estradiol intrauterine environments lead to abnormal expression of MEG3 and endothelium-derived factors. Meanwhile, silencing MEG3 expression decreased ET1 expression, and increased nitrite, nitrate, VEGF secretion, which could correct the effect we observed in-vivo. With pyrosequencing technology, we found that elevated expression of MEG3 in IVF offspring derived HUVECs was the result of hypomethylation of the MEG3 promoter. Conclusions: Our results demonstrated that higher expression of MEG3 in IVF-born HUVECs, accompanied by lower secretion of eNOS, VEGF, and higher secretion of ET1, which is closely related with endothelial dysfunction, which together provide a potential mechanism addressing high-risk of hypertension in IVF offspring.

Non-esterified fatty acids impair endothelium-dependent vasodilation in rat mesenteric resistance vessels

2004 ◽  
Vol 107 (6) ◽  
pp. 625-629 ◽  
Author(s):  
Christopher A. R. SAINSBURY ◽  
Naveed SATTAR ◽  
John M. C. CONNELL ◽  
Chris HILLIER ◽  
John R. PETRIE
Keyword(s):  
Fatty Acids ◽  
Ascorbic Acid ◽  
Endothelial Dysfunction ◽  
Palmitic Acid ◽  
Resistance Arteries ◽  
Response Curves ◽  
Esterified Fatty Acids ◽  
Increased Risk ◽  
Significant Impairment

Elevated circulating levels of NEFAs (non-esterified fatty acids) are associated with states of insulin resistance and increased risk of vascular disease. Previous animal and human studies have demonstrated NEFA-induced endothelial dysfunction of large conduit arteries, reversible by the antioxidant ascorbic acid. We therefore investigated the effect of NEFAs on carbachol-induced endothelium-dependent vasodilation of rat resistance arteries in vitro using the technique of wire myography. In addition, we investigated the effect of co-incubation of NEFAs and ascorbic acid. Cumulative concentration–response curves to carbachol (endothelium-dependent vasodilation) and SNAP (S-nitroso-N-acetyl-DL-penicillamine; endothelium-independent vasodilation) were constructed. Those to carbachol were repeated following a 30 min incubation with either oleic acid (10−4 M) or palmitic acid (10−4 M), demonstrating significant impairment of endothelium-dependent vasodilation with both [P<0.05, comparison of pD2 values (the negative log concentration of agonist required to effect a 50% response)]. A cumulative concentration–response curve to carbachol was repeated following co-incubation with palmitic acid (10−4 M) and the antioxidant ascorbic acid (10−5 M), demonstrating an abolition of the previously observed endothelial dysfunction induced by palmitic acid. There was no impairment of vasodilation to SNAP following NEFA incubation. We conclude that NEFAs directly impair endothelial function in rat resistance arteries via an increase in oxidative stress at the vascular endothelium.

Effects of propylthiouracil and methylmercaptoimidazole on thyroglobulin synthesis

1980 ◽  
Vol 93 (1) ◽  
pp. 32-36 ◽  
Author(s):  
F. Monaco ◽  
C. Santolamazza ◽  
I. De Ros ◽  
A. Andreoli
Keyword(s):  
Thyroid Tissue ◽  
In Vitro Experiments ◽  
In Vivo Experiments ◽  
Polypeptide Synthesis ◽  
Antithyroid Treatment ◽  
Significant Impairment ◽  
Antithyroid Agents ◽  
Carbohydrate Chains

Abstract. The effect of 6-propyl-2-thiouracil (PTU), and 1-methyl-2-mercaptoimidazole (MMI) on thyroglobulin (Tg) biosynthesis has been studied in vivo and in vitro. In vivo experiments were performed in rats treated for 20 days with PTU or MMI. analyzing soluble and particulate, cold and 125I-labelled, Tg. Thyroglobulin biosynthesis was also investigated by in vitro experiments, incubating thyroid tissue with labelled amino acid and carbohydrate in the presence of antithyroid compounds. It has been found that in vivo antithyroid agents decrease the amount of soluble Tg and increase the proportion of particulate Tg. Tg from treated animals is poorly iodinated being mainly represented by its 12S subunit. In vitro studies demonstrate that PTU and MMI inhibit Tg biosynthesis which is impaired in the polypeptide synthesis as wellas in carbohydrate chains addition. Thus the inhibition of the hormonogenetic processes induced by antithyroid treatment leading to a depressed iodinating activity also appears to be related to a significant impairment of the production of the Tg molecule, the specific iodine acceptor.

scholarly journals Elevated expression of lncRNA MEG3 induces endothelial dysfunction on HUVECs of IVF born offspring via epigenetic regulation

2020 ◽  
Author(s):  
Ying Jiang ◽  
Hong Zhu ◽  
Hong Chen ◽  
Meng-Meng Yang ◽  
Yi-Chen Yu ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Umbilical Vein ◽  
Methylation Status ◽  
Vitro Fertilization ◽  
In Vivo Experiments ◽  
Elevated Expression ◽  
Nitrite Nitrate ◽  
Umbilical Vein Endothelial Cells

Abstract Background: The cardiovascular dysfunction in children born after in vitro fertilization (IVF) has been of great concern, in our study, we aim to explore potential molecular mechanism for such long-term outcomes. Methods： Real-time qPCR was used to test long non-coding RNAMEG3and endothelium-derived factors, endothelial nitric oxide synthase (eNOS), endothelin-1(ET1), vascular endothelial growth factor (VEGF). Primary HUVEC after caesarean section was treated with different estradiol concentrations in vitro. Besides, knockdown ofMEG3on HUVEC provided further evidence between MEG3 expression and alteration of NO, ET1, VEGF. Then, by using pyrosequencing, we detectedMEG3promoter methylation status. Results: We found that the expression level of MEG3was higher in human umbilical vein endothelial cells (HUVECs) of IVF offspring than that in spontaneously born offspring. Furthermore, we found decreased expression ofeNOS, VEGF, elevated expression of ET1in HUVECs from IVF offspring compared to spontaneously born offspring. We further confirmed the results from in-vivo experiments by demonstrating that high-estradiol intrauterine environments lead to abnormal expression of MEG3 and endothelium-derived factors. Meanwhile, silencing MEG3expression decreased ET1expression, and increased nitrite, nitrate, VEGFsecretion, which could correct the effect we observed in-vivo. With pyrosequencing technology, we found that elevated expression of MEG3in IVF offspring derived HUVECs was the result of hypomethylation of the MEG3promoter. Conclusions: Our results demonstrated that higher expression ofMEG3in IVF-born HUVECs, accompanied by lower secretion of eNOS, VEGF, and higher secretion of ET1, which is closely related with endothelial dysfunction, which togetherprovide a potential mechanism addressing high-risk of hypertension in IVF offspring.

scholarly journals Restoration of endothelin-1-induced impairment in endothelium-dependent relaxation by interleukin-10 in murine aortic ringsThis article is one of a selection of papers published in the special issue (part 2 of 2) on Forefronts in Endothelin.

2008 ◽  
Vol 86 (8) ◽  
pp. 557-565 ◽  
Author(s):  
Saiprasad M. Zemse ◽  
Rob H.P. Hilgers ◽  
G. Bryan Simkins ◽  
R. Daniel Rudic ◽  
R. Clinton Webb
Keyword(s):  
Endothelial Dysfunction ◽  
Immunohistochemical Analysis ◽  
Interleukin 10 ◽  
Enos Expression ◽  
Short Term ◽  
Response Curves ◽  
Endothelin 1 ◽  
Short Term Exposure ◽  
Endothelium Dependent Relaxation ◽  
Antiinflammatory Cytokine

Endothelin-1 (ET-1) is implicated in the development of endothelial dysfunction through the generation of reactive oxygen species by NADPH oxidase activation. Interleukin-10 (IL-10) is an antiinflammatory cytokine that stimulates nitric oxide production, decreases superoxide production, and restores endothelial integrity after vascular injury. In this study, we tested whether IL-10 attenuates ET-1-induced endothelial dysfunction by improving acetylcholine (ACh)-induced relaxation of cultured murine aortic rings. Aortic rings (2 mm long) of C57BL/6 mice were incubated in 2 mL DMEM containing 120 U/mL penicillin and 120 μg/mL streptomycin in the presence of one of 4 treatments: vehicle (deionized water), ET-1 (100 nmol/L), recombinant mouse IL-10 (300 ng/mL), or a combination of both ET-1 and IL-10. After incubation at 37 °C for either 1 or 6 h (short-term exposure) or 22 h (overnight exposure), rings were mounted in a wire myograph and stretched to a passive force of 5 mN. Endothelium-dependent vasorelaxation was assessed by constructing cumulative concentration–response curves to ACh (0.001–10 μmol/L) during 10 μmol/L phenylephrine (PE)-induced contraction. Short-term exposure of ET-1 did not result in an impairment of ACh-induced relaxation. Overnight exposure of aortic rings to ET-1 resulted in a statistically significant endothelial dysfunction characterized by a reduced maximal relaxation response to ACh compared with that of untreated rings (Emax 57% ± 3% versus 82% ± 4%). IL-10 treatment restored ACh-induced relaxation (Emax 77% ± 3%). Western blotting showed decreased eNOS expression in response to ET-1, whereas vessels treated with a combination of ET-1 and IL-10 showed increased expression of eNOS. Immunohistochemical analysis showed decreased eNOS expression in ET-1-treated vessels compared with those treated with both ET-1 and IL-10. We conclude that, in murine aorta, the antiinflammatory cytokine IL-10 prevents impairment in endothelium-dependent relaxation induced in response to long-term incubation with ET-1 via normalization of eNOS expression.

scholarly journals LysGH15 Effectively Control Murine Mastitis Caused by Staphylococcus aureus

2020 ◽  
Vol 40 (04) ◽  
pp. 519-522
Author(s):  
Yalu Ji
Keyword(s):  
Staphylococcus Aureus ◽  
Breast Tissue ◽  
Bovine Mastitis ◽  
Gram Positive Bacteria ◽  
In Vivo Experiments ◽  
Tnf Α ◽  
A Cell ◽  
Phage Lysin

Bovine mastitis is an inflammatory response mainly caused by Staphylococcus aureus. Lysin is a cell wall hydrolase encoded and synthesized by a bacteriophage, which can kill specific Gram-positive bacteria. In this study, phage lysin “LysGH15” is used to treat the mice mastitis caused by S. aureus. The purified lysGH15 showed strong bactericidal activity in vitro. When treated with 25μg/mL of the LysGH15, the bacterial counts of S. aureus dropped approximately 5 log units within 10 min. In the in vivo experiments, the administration of LysGH15 significantly (P<0.05) reduced the colonies of S. aureus and alleviated damage to the breast tissue. Also, the levels of IL-6 and TNF-α in breast tissue were significantly decreased. It indicates that the LysGH15 can effectively treat the murine mastitis caused by S. aureus. This study demonstrated the potential of LysGH15 as an alternative to antibiotics for treating bovine mastitis caused by S. aureus

scholarly journals Host-Pathogen Interaction and Signaling Molecule Secretion Are Modified in thedpp3Knockout Mutant of Candida lusitaniae

2013 ◽  
Vol 82 (1) ◽  
pp. 413-422 ◽  
Author(s):  
Ayman Sabra ◽  
Jean-Jacques Bessoule ◽  
Vessela Atanasova-Penichon ◽  
Thierry Noël ◽  
Karine Dementhon
Keyword(s):  
Interleukin 10 ◽  
Gene Inactivation ◽  
Physical Contact ◽  
Knockout Mutant ◽  
Necrosis Factor Alpha ◽  
Content Type ◽  
Tnf Α ◽  
Candida Lusitaniae

ABSTRACTCandida lusitaniaeis an emerging opportunistic yeast and an attractive model to discover new virulence factors inCandidaspecies by reverse genetics. Our goal was to create adpp3Δ knockout mutant and to characterize the effects of this gene inactivation on yeastin vitroandin vivointeraction with the host. The secretion of two signaling molecules inCandidaspecies, phenethyl alcohol (PEA) and tyrosol, but not of farnesol was surprisingly altered in thedpp3Δ knockout mutant. NO and reactive oxygen species (ROS) production as well as tumor necrosis factor alpha (TNF-α) and interleukin 10 (IL-10) secretion were also modified in macrophages infected with this mutant. Interestingly, we found that the wild-type (WT) strain induced an increase in IL-10 secretion by zymosan-activated macrophages without the need for physical contact, whereas thedpp3Δ knockout mutant lost this ability. We further showed a striking role of PEA and tyrosol in this modulation. Last, theDPP3gene was found to be an essential contributor to virulence in mice models, leading to an increase in TNF-α secretion and brain colonization. Although reinsertion of a WTDPP3copy in thedpp3Δ knockout mutant was not sufficient to restore the WT phenotypesin vitro, it allowed a restoration of those observedin vivo. These data support the hypothesis that some of the phenotypes observed followingDPP3gene inactivation may be directly dependent onDPP3, while others may be the indirect consequence of another genetic modification that systematically arises when theDPP3gene is inactivated.

ANTITUMOR EFFECT OF COLLOIDAL SILVER BISILICATE IN EXPERIMENTAL IN VITRO AND IN VIVO STUDIES

2019 ◽  
Vol 65 (5) ◽  
pp. 760-765
Author(s):  
Margarita Tyndyk ◽  
Irina Popovich ◽  
A. Malek ◽  
R. Samsonov ◽  
N. Germanov ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Tumor Growth ◽  
Tumor Cells ◽  
Human Tumor ◽  
Significant Inhibition ◽  
In Vivo Studies ◽  
Ehrlich Carcinoma ◽  
In Vivo Experiments

The paper presents the results of the research on the antitumor activity of a new drug - atomic clusters of silver (ACS), the colloidal solution of nanostructured silver bisilicate Ag6Si2O7 with particles size of 1-2 nm in deionized water. In vitro studies to evaluate the effect of various ACS concentrations in human tumor cells cultures (breast cancer, colon carcinoma and prostate cancer) were conducted. The highest antitumor activity of ACS was observed in dilutions from 2.7 mg/l to 5.1 mg/l, resulting in the death of tumor cells in all studied cell cultures. In vivo experiments on transplanted Ehrlich carcinoma model in mice consuming 0.75 mg/kg ACS with drinking water revealed significant inhibition of tumor growth since the 14th day of experiment (maximally by 52% on the 28th day, p < 0.05) in comparison with control. Subcutaneous injections of 2.5 mg/kg ACS inhibited Ehrlich's tumor growth on the 7th and 10th days of the experiment (p < 0.05) as compared to control.

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