scholarly journals Paracrine and endocrine actions of interferon tau (IFNT)

Reproduction ◽  
2017 ◽  
Vol 154 (5) ◽  
pp. F45-F59 ◽  
Author(s):  
Thomas R Hansen ◽  
Leticia D P Sinedino ◽  
Thomas E Spencer

This review focuses on the paracrine and endocrine actions of interferon tau (IFNT) during pregnancy recognition and establishment in ruminants. Pregnancy recognition involves the suppression of the endometrial luteolytic mechanism by the conceptus to maintain progesterone production by the corpus luteum (CL). The paracrine antiluteolytic effects of conceptus-derived IFNT inhibit upregulation of oxytocin receptors in the endometrial epithelia of the uterus, thereby preventing the production of luteolytic prostaglandin F2 alpha (PGF2α) pulses. In the endometrium, IFNT induces or upregulates a large number of classical IFN-stimulated genes (ISGs) and regulates expression of many other genes in a cell-specific manner that are likely important for conceptus elongation, implantation and establishment of pregnancy. Further, IFNT has endocrine effects on extrauterine cells and tissues. In sheep, IFNT induces luteal resistance to PGF2α, thereby ensuring survival of the CL for maintenance of pregnancy. The ISGs induced in circulating peripheral blood mononuclear cells by IFNT may also be useful as an indicator of pregnancy status in cattle. An increased knowledge of IFNT and ISGs is important to improve the reproductive efficiency in ruminants.

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Natsumi Funeshima ◽  
Ryotaro Miura ◽  
Taiga Katoh ◽  
Hikari Yaginuma ◽  
Takeshi Kitou ◽  
...  

Abstract Background Repeat breeding is a critical reproductive disorder in cattle. The problem of repeat breeder cattle remains largely unmanageable due to a lack of informative biomarkers. Here, we utilized metabolomic profiling in an attempt to identify metabolites in the blood plasma and uterine luminal fluids. We collected blood and uterine fluid from repeat breeder and healthy cows on day 7 of the estrous cycle. Results Metabolomic analysis identified 17 plasma metabolites detected at concentrations that distinguished between the two groups, including decreased various bile acids among the repeat breeders. However, no metabolites that varied significantly were detected in the uterine luminal fluids between two groups. Among the plasma samples, kynurenine was identified as undergoing the most significant variation. Kynurenine is a metabolite produced from tryptophan via the actions of indoleamine 2,3-dioxygenase (IDO). As IDO is key for maternal immune tolerance and induced in response to interferon tau (IFNT, ruminant maternal recognition of pregnancy factor), we examined the responsiveness to IFNT on peripheral blood mononuclear cells (PBMC) isolated from healthy and repeat breeder cows. The mRNA expression of IFNT-response makers (ISG15 and MX2) were significantly increased by IFNT treatment in a dose-dependent manner in both groups. Although treatment with IFNT promoted the expression of IDO in PBMCs from both groups, it did so at a substantially reduced rate among the repeat breeder cows, suggesting that decreased levels of kynurenine may relate to the reduced IDO expression in repeat breeder cows. Conclusions These findings provide valuable information towards the identification of critical biomarkers for repeat breeding syndrome in cattle.


2021 ◽  
Vol 2021 ◽  
pp. 1-6
Author(s):  
Alicja Kowalczyk ◽  
Ewa Czerniawska-Piątkowska ◽  
Marcjanna Wrzecińska

Several decades of improving dairy cattle towards unilateral utilization of dairy cattle led to enormous progress in the field of milk yield; however, it resulted in a number of unfavorable features, such as reproductive disorders, increased calf mortality, and reduced health. Most cases of embryo loss and/or lost pregnancies occur during the first four to five weeks of gestation; accurate detection for pregnancy during this period is likely to contribute to an improvement in gestation rates. A specific protein, interferon-tau (IFNT), stimulates interferon-stimulated genes (ISGs), and their expression increases during gestation within 21 days after insemination. In bovines, the early conceptus undergoes a phase of rapid growth and elongation before implantation, the latter occurring 2–3 weeks after fertilization. IFNT acts mainly in the endometrium of the luminal epithelium. It is a new type I interferon that regulates several genes encoding uterine-derived factors. They are crucial in the processes of preparing the uterus for placenta attachment, modifying the uterine immune system, and regulating early fetal development. Because IFNT is expressed and induces ISGs in the endometrium during pregnancy recognition, it was reasoned that surrogate markers for pregnancy or IFNT might be present in the blood and provide an indicator of pregnancy status in cattle.


Author(s):  
Petrungaro A ◽  
◽  
Scudo F ◽  
Quartarone E ◽  
◽  
...  

The implant of autologous mononuclear cells is an avant-garde method based on the use of a cell population within our body to regenerate tissues that have been damaged by various pathological events. The biological assumption is the richness and complexity of biochemical and cellular phenomena inherent in both organism response to damage and tissue regeneration. The key role is played by the mononuclear phagocyte system which regulates and modulates the activity of mesenchymal stem cells capable of differentiating and providing tissue repair. This system does not only have a traditional “scavenger” function within the immune system, but it is also of central importance in the modulation and activation of the response to tissue damage, be it traumatic, surgical, or degenerative. In this review we summarize the main features of this method and the most common uses in clinical practice where the interest is growing considering both the powerful, rapid and documented regenerative response of the various “target” tissues: vascular, cartilage, bone, muscle and tendon tissue.


2017 ◽  
Vol 43 (4) ◽  
pp. 1515-1525 ◽  
Author(s):  
Bailing Li ◽  
Wei Zhou ◽  
Xiaojun Tang ◽  
Wei Wang ◽  
Jiajun Pan ◽  
...  

Background/Aims: The imbalance of Treg/Th17 cells plays important role in the pathogenesis of dilated cardiomyopathy (DCM). Response gene to complement (RGC)-32 is a cell cycle regulator that plays an important role in cell proliferation. We evaluated whether the upregulation of RGC-32 was implicated in the homeostasis of Treg/Th17 cells in DCM. Methods: The levels of plasma RGC-32, IL-17 and TGF-β1, and the frequencies of circulating CD4+ RGC-32+ T cells, Th17 and Treg cells in patients with DCM were determined by Cytokine-specific sandwich ELISA and the flow cytometer (FCM), respectively. Results: A significant elevation of plasma RGC-32 in patients with DCM compared with healthy control (HC) subjects was observed. This upregulation was associated with an increase in frequency of Th17 and a decrease in frequency of Treg cells. To further assessed the role of RGC-32, we investigated the effects of RGC-32 up- or down-regulation on frequencies of Th17 and Treg cells in peripheral blood mononuclear cells (PBMCs) from subjects. Importantly, overexpression of RGC-32 was accompanied by an augmentation of Th17 and a reduction of Treg expression. Conclusion: In summary, our study demonstrated the up-regulation of RGC-32 contributed to the imbalance of Treg/Th17 cells in patients with DCM.


2021 ◽  
Vol 22 (20) ◽  
pp. 11173
Author(s):  
Ioanna Kokkinopoulou ◽  
Andriana Diakoumi ◽  
Paraskevi Moutsatsou

Stress and depression increase the risk of Type 2 Diabetes (T2D) development. Evidence demonstrates that the Glucocorticoid (GC) negative feedback is impaired (GC resistance) in T2D patients resulting in Hypothalamic-Pituitary-Adrenal (HPA) axis hyperactivity and hypercortisolism. High GCs, in turn, activate multiple aspects of glucose homeostasis in peripheral tissues leading to hyperglycemia. Elucidation of the underlying molecular mechanisms revealed that Glucocorticoid Receptor (GR) mediates the GC-induced dysregulation of glucose production, uptake and insulin signaling in GC-sensitive peripheral tissues, such as liver, skeletal muscle, adipose tissue, and pancreas. In contrast to increased GR peripheral sensitivity, an impaired GR signaling in Peripheral Blood Mononuclear Cells (PBMCs) of T2D patients, associated with hyperglycemia, hyperlipidemia, and increased inflammation, has been shown. Given that GR changes in immune cells parallel those in brain, the above data implicate that a reduced brain GR function may be the biological link among stress, HPA hyperactivity, hypercortisolism and hyperglycemia. GR polymorphisms have also been associated with metabolic disturbances in T2D while dysregulation of micro-RNAs—known to target GR mRNA—has been described. Collectively, GR has a crucial role in T2D, acting in a cell-type and context-specific manner, leading to either GC sensitivity or GC resistance. Selective modulation of GR signaling in T2D therapy warrants further investigation.


2003 ◽  
Vol 77 (13) ◽  
pp. 7444-7451 ◽  
Author(s):  
P. V. Jensen ◽  
Y. Castelruiz ◽  
B. Aasted

ABSTRACT The aim of this study was to examine the levels of gamma interferon (IFN-γ)-, interleukin 4 (IL-4)-, and IL-8-producing cells in peripheral blood mononuclear cells from mink infected with the Aleutian mink disease parvovirus (ADV). As expected, ADV-infected mink developed high plasma gamma globulin values (hypergammaglobulinemia) and enhanced quantities of CD8-positive (CD8+) cells in the blood during the infection. We quantified the percentages of IFN-γ- and IL-4-positive lymphocytes and IL-8-positive monocytes up to week 38 after virus challenge. The results clearly indicated marked increases in the percentages of IFN-γ- and IL-4-producing lymphocytes during ADV infection. The total number of IL-8-producing monocytes in the blood of ADV-infected mink stayed fairly constant during the infection. In order to characterize the phenotype of the cytokine-producing cells, we performed double-labeling fluorescence-activated cell sorter (FACS) experiments with CD8 surface labeling in one channel and cytokine intracellular staining in the other. We found that most IFN-γ and IL-4 in ADV-infected mink was produced by CD8+ cells, while in the uninfected mink, these cytokines were primarily produced by a cell type that was not CD8 (possibly CD4-positive cells). We also observed that IL-8 was almost exclusively produced by monocytes. All of the above findings led us to conclude that both Th1- and Th2-driven immune functions are found in mink plasmacytosis.


2011 ◽  
Vol 23 (1) ◽  
pp. 162
Author(s):  
N. Mansouri-Attia ◽  
L. J. Oliveira ◽  
F. Carter ◽  
N. Forde ◽  
P. Lonergan ◽  
...  

During the bovine peri-implantation period, immune cells are exposed to endocrine and paracrine signals, which support feto-placental development. Recent studies in cattle have shown that the antiviral factor Mx2, known to be up-regulated by conceptus-derived interferon-τ in pregnancy, is detected in peripheral blood mononuclear cells (PBMC) and can be used for pregnancy detection on Day 18. The objectives of the current study were to correlate mRNA expression levels of pregnancy associated factors and immune modulators RSAD2 (radical S-adenosyl methionine domain containing-2) and TGF-β (transforming growth factor β) in circulating PBMCs, with pregnancy status in dairy cows and heifers. Holstein-Friesian heifers (n = 12) and lactating dairy cows (n = 17) were synchronised to estrus and artificially inseminated (bred) or not (non bred, n = 4). Blood samples were collected on Day 0 (day of AI or estrus), 5, 7, 13, 16, 20, and 25 for PBMC isolation. Pregnancy was diagnosed retrospectively by transrectal ultrasonography at Days 30 and 60 after breeding. The relative quantification of RSAD2 and TGF-β transcript abundance, analysed by qPCR, was normalised against PPIA and calculated according to the relative standard curve method. Data from duplicates were pooled, and a mixed model was run on the pooled Cq values for each stage. Genes were considered as differentially expressed if the mixed model P value was <0.05. RSAD2 mRNA abundance was 2-fold higher in pregnant heifers compared with non-bred heifers on Day 20 (P < 0.01) and Day 25 (P < 0.03) post AI. Likewise, RSAD2 mRNA expression was greater (2.25 fold) in pregnant heifers compared with heifers that were inseminated but not pregnant (P < 0.007). In contrast, RSAD2 expression was not significantly different in pregnant cows compared to non-bred or bred but non-pregnant cows. TGF-β mRNA abundance was significantly lower in both pregnant cows (3.5-fold, P < 0.04) and pregnant heifers (4.5-fold, P < 0.01) compared to non-bred animals as early as Day 13. This suppression of expression was maintained until Day 20 in heifers (3.9-fold, P < 0.02). In addition, PBMC TGF-β mRNA expression was lower in pregnant cows compared with bred non-pregnant cows (1.65-fold, P < 0.06). In conclusion, Day 20 PBMC RSAD2 expression may be a useful predictor of pregnancy maintenance in dairy heifers. However, decreased TGF-β expression as early as Day 13 appears to be a more powerful indicator of the presence of a viable embryo in both dairy heifers and cows and may play a role in the establishment and maintenance of pregnancy through the restriction of monocyte recruitment or activation during the time of maternal recognition of pregnancy. Research supported by Science Foundation Ireland (PICA-B813)


Reproduction ◽  
2008 ◽  
Vol 136 (4) ◽  
pp. 481-490 ◽  
Author(s):  
Lilian J Oliveira ◽  
P J Hansen

The presence of conceptus alloantigens necessitates changes in maternal immune function. Here, we used the cow to evaluate whether species with epitheliochorial placentation have changes in specific leukocyte populations during pregnancy similar to those reported in species with hemotropic placentae. At days 33–34 of pregnancy, there was no effect of pregnancy status on the number of cells positive for CD8, CD4, γδT cell receptor, or the monocyte marker CD68 in the peripheral blood mononuclear cell (PBMC) population. There was, however, an increase in the proportion of CD4+cells that were positive for CD25. There was no effect of status on the proportion of PBMCs that were CD8+when comparing preparturient cows to nonpregnant cows. However, preparturient cows had an increased percentage of PBMCs that were γδT cells and CD4+CD25+and a tendency for a lower percentage that were CD68+cells. Using immunolocalization with anti-CD68, it was found that pregnant cows had increased numbers of CD68+cells in the endometrial stroma as early as days 54–100 of gestation; this increase persisted through the last time examined (day 240 of gestation). Cells positive for CD68 were also positive for another macrophage/monocyte marker, CD14. In conclusion, pregnancy in the cow is associated with changes in peripheral and endometrial leukocyte numbers, which are similar to patterns observed in other species.


1992 ◽  
Vol 3 (5) ◽  
pp. 279-282 ◽  
Author(s):  
D. W. Dixon ◽  
M. S. Kim ◽  
V. Kumar ◽  
G. Obara ◽  
L. G. Marzilli ◽  
...  

A series of amino- and hydroxytetraphenylporphyrin derivatives was found to have activity against the human immunodeficiency virus type 1 (HIV-1) in human peripheral blood mononuclear cells. Activity tends to be associated with increased hydrophilicity of the porphyrins for the porphyrins with one substituent on each phenyl ring but there is no clear pattern for the porphyrins with two substituents on each phenyl ring. The antiviral activity of certain porphyrins has been demonstrated in the absence of light, suggesting a non-photochemical process. Whereas only some of the porphyrins that inhibit HIV-1 in culture inhibit HIV-1 reverse transcriptase in a cell-free system, none of those tested inhibit DNA polymerase α.


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