TNF-α INDUCES THROMBOXANE RECEPTOR SIGNALING-DEPENDENT MICROCIRCULATORY DYSFUNCTION IN MOUSE LIVER

Myocardial infarction frequently occurs in the morning, a phenomenon in part resulting from the downregulation of fibrinolytic activity. Plasminogen activator inhibitor-1 (PAI-1) is a key factor behind fibrinolytic activity, and its gene expression is controlled under the circadian clock gene in the mouse heart and liver. Hypercholesterolemia has been associated with impaired fibrinolysis due to enhanced PAI-1 activity, which has also been implicated in atherosclerosis. The aim of this study was to decipher whether the Pai-1 gene is still expressed daily with hypercholesterolemia. Hypercholesterolemia (1% cholesterol diet) did not significantly affect the daily expression of clock genes ( Per2 and Bmal1) and clock-controlled genes ( Dbp and E4bp4) in the liver ( P > 0.05); however, daily expression of the Pai-1 gene and Pai-1 promoter regulating factor genes such as Nr4a1 was significantly upregulated ( P < 0.01). Daily restricted feeding for 4 h during the day reset the gene expression of Per2, Pai-1, Nr4a1, and Tnf-α. Lesion of the suprachiasmatic nucleus, the location of the main clock system, led to loss of Per2 and Pai-1 daily expression profiles. In the present experiments, we demonstrated that hypercholesterolemia enhanced daily expression of the Pai-1, Tnf-α, and Nr4a1 genes in the mouse liver without affecting clock and clock-controlled genes. Therefore, the risk or high frequency of acute atherothrombotic events in the morning still seems to be a factor that may be augmented under conditions of hypercholesterolemia.

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Virulence comparison of human and poultry Campylobacter jejuni isolates in a mouse model

Medical Research Archives ◽

10.18103/mra.v5i10.1581 ◽

2017 ◽

Vol 5 (10) ◽

Author(s):

Darinka Vučković ◽

Maja Šikić Pogačar ◽

Peter Raspor ◽

Maja Abram ◽

Sonja Smole Možina ◽

...

Keyword(s):

Campylobacter Jejuni ◽

Mouse Liver ◽

Virulence Genes ◽

Cytokine Production ◽

Host Responses ◽

Human Origin ◽

Tnf Α ◽

Food Isolate ◽

Ifn Γ ◽

Food Model

ABSTRACTObjective: Research into Campylobacter jejuni pathogenesis and host responses to C. jejuni infection is needed in the fight against human campylobacteriosis.Methods: We established intravenous infections of BALB/c mice with either a C. jejuni food isolate or C. jejuni of human origin. Further we include PCR to demonstrate the presence and stability of the putative virulence genes cadF, virbB11, cdtB, cdtC, ceuE in C. jejuni isolates and we examined cytokine production of IL-6, IL-12, TNF-α, IFN-γ, IL-10 in the livers of these infected mice.Results: We confirm here the presence of the cadF, cdtB, cdtC and ceuE genes in a food and a clinical C. jejuni isolate, with no sequence changes after the C. jejuni sub-culturing in a food model and when recovered from mouse liver after infection. Both of these C. jejuni isolates persisted in the mouse livers and activated comparable cytokine patterns for IL-12, TNF-α, IFN-γ and IL-10, with down-regulation of IL-6.Conclusions: These data show the comparability of these C. jejuni food and clinical isolates in terms of the prevalence and stability of their putative virulence genes and the outcome of disease during systemic murine campylobacteriosis.

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Monocyte-derived Macrophages: the Supplements of Hepatic Macrophage in Echinococcus Multilocularis Infected Mice

10.21203/rs.3.rs-20558/v1 ◽

2020 ◽

Author(s):

Bin Li ◽

Xinwei Qi ◽

Yumei Liu ◽

Yi Yan ◽

Jiaoyu Shan ◽

...

Keyword(s):

Flow Cytometry ◽

Persistent Infection ◽

Echinococcus Multilocularis ◽

Peripheral Blood ◽

Mouse Liver ◽

Qrt Pcr ◽

Tnf Α ◽

Mice Liver ◽

Experimental Group ◽

Hepatic Macrophage

Abstract Background Alveolar echinococcosis (AE) is a potentially lethal zoonosis caused by the cestode Echinococcus multilocularis. The aim of this study is to study the dynamic changes of monocytes, macrophages and related cytokines in animal models of persistent infection of Echinococcus multilocularis. To explore the possible connection between them and the persistent infection of Echinococcus multilocularis.Methods An infection model was established by intraperitoneal injection of a protoscolex suspension. The pathological changes of mice liver were observed by HE staining and the score scale of infection was established. The ratio of Ly6Chi and Ly6Clo Monocytes in peripheral blood of mice was detected by flow cytometry. The distribution and expression of CX3CL1, CX3CR1, iNOS, CD163 and CD11b in mouse liver were detected by immunohistochemistry. The mRNA expression levels of TNF-α and Arg1 in mouse liver were detected by qRT-PCR. The expression levels of INF-γ, IL-17, IL-4 and IL-10 in peripheral blood of mice were detected by ELISA.Results The results of HE staining showed that in the later stages of infection, significant lesions appear in the liver.The results of the infection degree score scale show that with the extension of the infection time, the severity score value increases. The results of flow cytometry showed that the proportion of Ly6Chi monocytes in the peripheral blood of the experimental group mice was decreased after a brief rise, Ly6Clo monocytes decreased first and then increased.. The results of immunohistochemistry showed that the expression of CX3CL1, CX3CR1, CD11b , CD163 and iNOS in the mice liver of the experimental group was increased. The results of qRT-PCR showed that the expression level of TNF-α and Arg1 mRNA in the liver of the experimental group mice were increased. The results of ELISA showed that the expression level of IFN-γ, IL-17, IL-4 and IL-10 increased with the duration of infection.Conclusions Monocytes as a supplement to hepatic macrophage, it and kupffer cells (KCs) participate in Th1 and Th2 immune responses of the body by differentiating into M1 or M2 at different stages of Echinococcus multilocularis infection.

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Changes in airway resistance by simultaneous exposure to TNF-α and IL-1β in perfused rat lungs

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.2001.280.4.l595 ◽

2001 ◽

Vol 280 (4) ◽

pp. L595-L601 ◽

Cited By ~ 13

Author(s):

Christian Martin ◽

Andrea Wohlsen ◽

Stefan Uhlig

Keyword(s):

Airway Resistance ◽

Simultaneous Exposure ◽

Inflammatory Conditions ◽

Thromboxane Receptor ◽

Rat Lungs ◽

Tnf Α ◽

Steroid Sensitive ◽

Cox 2 ◽

Thromboxane Receptor Antagonist ◽

Necrosis Factor

Tumor necrosis factor (TNF)-α and interleukin (IL)-1β are formed simultaneously under inflammatory conditions such as asthma and acute respiratory distress syndrome. Here we investigated the effects of TNF-α (10 ng/ml) and/or IL-1β (10 ng/ml) in isolated blood-free perfused rat lungs. In lungs precontracted with methacholine, IL-1β alone and IL-1β/TNF-α decreased airway resistance 10 min after administration, whereas TNF-α alone had no effect. In untreated lungs, airway resistance was unaltered by either cytokine alone but started to increase 40 min after treatment with both cytokines together, indicating bronchoconstriction. The bronchoconstriction was accompanied by a steroid-sensitive increase in cyclooxygenase (COX)-2 mRNA expression and thromboxane formation. The cytokine-induced bronchoconstriction was blocked by the thromboxane receptor antagonist SQ-29548, indomethacin, the selective COX-2 inhibitor NS-398, and the steroid dexamethasone. We conclude that IL-1β has an early bronchodilatory effect (after 10 min) that is unchanged by TNF-α. However, at later time points (after 40 min), IL-1β and TNF-α in concert cause a COX-2- and thromboxane-dependent bronchoconstriction. Our findings show that TNF-α and IL-1β exert complex and time-dependent effects on lung functions that cannot be predicted by studying each cytokine alone.

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