scholarly journals Leptin, a tool of parasites?

2012 ◽  
Vol 8 (5) ◽  
pp. 849-852 ◽  
Author(s):  
Mare Lõhmus ◽  
Sharon Moalem ◽  
Mats Björklund

One common physiological phenomenon that is involved both in infectious and in malignant processes is the reduction in appetite: disease anorexia. An increase in plasma levels of leptin with inflammation is thought to be involved in this process. However, from an evolutionary perspective, in certain cases, it would be more adaptive for an internal parasite to stimulate the appetite of the host instead of causing its suppression. We tested whether a parasitic infection with the larvae of the helminth parasite Taenia taeniaformis affects the levels of appetite-regulating proteins, such as leptin, ghrelin and neuropeptide-Y (NPY) in wild yellow-necked mouse ( Apodemus flavicollis ). We found that infected mice had lower plasma levels of leptin and increased levels of NPY than the uninfected subjects. Ghrelin levels were not associated with the occurrence of the parasites; however, these levels strongly correlated with the levels of NPY. This study suggests a possible manipulation by parasitic larvae of appetite regulation in infected subjects.

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1819
Author(s):  
Tatyana Karamysheva ◽  
Svetlana Romanenko ◽  
Alexey Makunin ◽  
Marija Rajičić ◽  
Alexey Bogdanov ◽  
...  

The gene composition, function and evolution of B-chromosomes (Bs) have been actively discussed in recent years. However, the additional genomic elements are still enigmatic. One of Bs mysteries is their spatial organization in the interphase nucleus. It is known that heterochromatic compartments are not randomly localized in a nucleus. The purpose of this work was to study the organization and three-dimensional spatial arrangement of Bs in the interphase nucleus. Using microdissection of Bs and autosome centromeric heterochromatic regions of the yellow-necked mouse (Apodemus flavicollis) we obtained DNA probes for further two-dimensional (2D)- and three-dimensional (3D)- fluorescence in situ hybridization (FISH) studies. Simultaneous in situ hybridization of obtained here B-specific DNA probes and autosomal C-positive pericentromeric region-specific probes further corroborated the previously stated hypothesis about the pseudoautosomal origin of the additional chromosomes of this species. Analysis of the spatial organization of the Bs demonstrated the peripheral location of B-specific chromatin within the interphase nucleus and feasible contact with the nuclear envelope (similarly to pericentromeric regions of autosomes and sex chromosomes). It is assumed that such interaction is essential for the regulation of nuclear architecture. It also points out that Bs may follow the same mechanism as sex chromosomes to avoid a meiotic checkpoint.


2009 ◽  
Vol 59 (2) ◽  
pp. 169-187 ◽  
Author(s):  
Michal Kozakiewicz ◽  
Alicja Gryczyńska–Siemiątkowska ◽  
Hanna Panagiotopoulou ◽  
Anna Kozakiewicz ◽  
Robert Rutkowski ◽  
...  

AbstractHabitat barriers are considered to be an important factor causing the local reduction of genetic diversity by dividing a population into smaller sections and preventing gene flow between them. However, the “barrier effect” might be different in the case of different species. The effect of geographic distance and water barriers on the genetic structure of populations of two common rodent species – the yellow-necked mouse (Apodemus flavicollis) and the bank vole (Myodes glareolus) living in the area of a lake (on its islands and on two opposite shores) was investigated with the use of microsatellite fragment analysis. The two studied species are characterised by similar habitat requirements, but differ with regard to the socio-spatial structure of the population, individual mobility, capability to cross environmental barriers, and other factors. Trapping was performed for two years in spring and autumn in north-eastern Poland (21°E, 53°N). A total of 160 yellow-necked mouse individuals (7 microsatellite loci) and 346 bank vole individuals (9 microsatellite loci) were analysed. The results of the differentiation analyses (FST and RST) have shown that both the barrier which is formed by a ca. 300 m wide belt of water (between the island and the mainland) and the actual distance of approximately 10 km in continuous populations are sufficient to create genetic differentiation within both species. The differences between local populations living on opposite lake shores are the smallest; differences between any one of them and the island populations are more distinct. All of the genetic diversity indices (the mean number of alleles, mean allelic richness, as well as the observed and expected heterozygosity) of the local populations from the lakeshores were significantly higher than of the small island populations of these two species separated by the water barrier. The more profound “isolation effect” in the case of the island populations of the bank vole, in comparison to the yellow-necked mouse populations, seems to result not only from the lower mobility of the bank vole species, but may also be attributed to other differences in the animals' behaviour.


2021 ◽  
Author(s):  
Fengmei Wang ◽  
Jirong Yu ◽  
Lei zhang ◽  
Yan Zhang ◽  
Jie Zhang ◽  
...  

Abstract Background The aim of the study was to investigate the clinical relevance of IgM deposition in patients with LN in a large cohort. Results 217 patients with renal biopsy–proven lupus nephritis were enrolled. The associations between glomerular IgM deposition and clinicopathological parameters were further analyzed. IgM deposition was positively correlated with glomerular C1q and C3 deposition moderately (r = 0.436, P < 0.001; r = 0.408, P < 0.001, respectively), and inversely correlated with plasma levels of C3 and CFH mildly (r=-0.138, P = 0.043; r=-0.147, P = 0.037, respectively). By multivariate analysis, we found that glomerular IgM deposition independently contributes to glomerular C3 deposition in patients with lupus nephritis (OR = 2.002, 95% CI: 1.295–3.094, P = 0.002). In addition, we also found that patients with IgM 0+-2 + had similar plasma CFH levels, but in patients with IgM3+-4+, plasma CFH levels were significantly lower (300.4 ± 155.8µg/ml vs. 429.9 ± 187.5µg/ml, P < 0.001). Furthermore, patients with high density of glomerular IgM and low levels of CFH had heavier proteinuria, higher serum creatinine and lower plasma C3 levels (5.7 ± 3.1g/d vs. 4.7 ± 3.5g/d, P = 0.037;150.1 ± 121.0µmol/L vs. 105.6 ± 97.1µmol/L, P = 0.005; 0.3 ± 0.2µg/L vs. 0.4 ± 0.2µg/L, P = 0.04, respectively), comparing with those with low density of glomerular IgM and low levels of CFH. Conclusions Our results suggested IgM might bind to injury-associated epitopes and be involved in disease progression and provided a possible relevance of CFH and IgM in the process of alternative pathway (AP) activation.


2012 ◽  
Vol 32 (suppl_1) ◽  
Author(s):  
Heather M Perry ◽  
Amanda Doran ◽  
Stephanie N Oldham ◽  
Ayelet Gonen ◽  
Xuchu Que ◽  
...  

Background: The HLH transcription factor, Id3, is essential for B cell-mediated atheroprotection in mice and a functionally significant single nucleotide polymorphism in the human ID3 gene at rs11574 is associated with carotid intimal medial thickness in humans. Yet, the mechanisms mediating Id3 atheroprotection are poorly understood. Recent studies provide clear evidence that B cell effects on atherosclerosis are subset dependent; with B2 cells promoting and B-1a cells attenuating atherosclerosis in a sIgM-dependent manner. Innate, natural IgM antibodies, such as E06, recognize oxidized phospholipids, are produced by B-1a cells, and inhibit atherogenesis. Therefore, we hypothesized that Id3 would regulate plasma levels of E06 IgM and atheroprotective B-1a cells. Methods & Results: Id3 -/- ApoE -/- mice (n = 9) at 8 weeks old had lower plasma levels of E06 compared to control Id3 +/+ ApoE -/- mice (n = 9) (1500 vs. 2750 RLU, p < 0.05) as measured by ELISA. This was not due to lower total IgM (270 vs. 100 ug/mL respectively, p < 0.05). ApoB-100 levels were not different (1500 vs 1600 RLU, n.s.). Consistent with plasma data, the number of B-1a cells, assessed by flow cytometry, was lower in Id3 -/- ApoE -/- (n = 5) compared to Id3 +/+ ApoE -/- mice (n = 4) (0.8 x10 5 vs 3.0 x10 5 , p < 0.05). There was no difference in transcript levels, as measured by real-time PCR, of E06 or sIgM in fluorescence-activated cell sorted B-1a cells. Furthermore, we found decreased homeostatic proliferation, measured by in situ CFSE dilution, of B-1a cells in Id3 -/- ApoE -/- mice (n = 5) compared to control mice (n = 5) (30.1% vs. 50.0%, p = 0.001). Additionally, humans with the functionally significant polymorphism in ID3 had lower plasma levels of IgM to MDA-LDL (n = 97, trend with p = 0.08) and no difference in IgG as measured by ELISA. Conclusion: Taken together, these data suggest a novel role for Id3 in regulating B-1a cell proliferation, resulting in reduced plasma levels of the atheroprotective natural antibody, E06. Moreover, the data suggest that the ID3 polymorphism in humans at rs11574 may link protective IgM to modified lipids with vascular disease.


2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Dragana Miloradovic ◽  
Dragica Miloradovic ◽  
Bojana Simovic Markovic ◽  
Aleksandar Acovic ◽  
Carl Randall Harrell ◽  
...  

There is still a lively debate about whether mesenchymal stem cells (MSCs) promote or suppress antitumor immune response. Although several possible explanations have been proposed, including different numbers of injected and engrafted MSCs, heterogeneity in phenotype, and function of tumor cells, the exact molecular mechanisms responsible for opposite effects of MSCs in modulation of antitumor immunity are still unknown. Herewith, we used a B16F10 murine melanoma model to investigate whether timing of MSC administration in tumor-bearing mice was crucially important for their effects on antitumor immunity. MSCs, intravenously injected 24 h after melanoma induction (B16F10+MSC1d-treated mice), significantly enhanced natural killer (NK) and T cell-driven antitumor immunity, suppressed tumor growth, and improved survival of melanoma-bearing animals. Significantly higher plasma levels of antitumorigenic cytokines (TNF-α and IFN-γ), remarkably lower plasma levels of immunosuppressive cytokines (TGF-β and IL-10), and a significantly higher number of tumor-infiltrating, IFN-γ-producing, FasL- and granzyme B-expressing NK cells, IL-17-producing CD4+Th17 cells, IFN-γ- and TNF-α-producing CD4+Th1 cells, and CD8+cytotoxic T lymphocytes (CTLs) were observed in B16F10+MSC1d-treated mice. On the contrary, MSCs, injected 14 days after melanoma induction (B16F10+MSC14d-treated mice), promoted tumor growth by suppressing antigen-presenting properties of tumor-infiltrating dendritic cells (DCs) and macrophages and by reducing tumoricidal capacity of NK cells and T lymphocytes. Significantly higher plasma levels of TGF-β and IL-10, remarkably lower plasma levels of TNF-α and IFN-γ, and significantly reduced number of tumor-infiltrating, I-A-expressing, and IL-12-producing macrophages, CD80- and I-A-expressing DCs, granzyme B-expressing CTLs and NK cells, IFN-γ- and IL-17-producing CTLs, CD4+Th1, and Th17 cells were observed in B16F10+MSC14d-treated animals. In summing up, the timing of MSC administration into the tumor microenvironment was crucially important for MSC-dependent modulation of antimelanoma immunity. MSCs transplanted during the initial phase of melanoma growth exerted tumor-suppressive effect, while MSCs injected during the progressive stage of melanoma development suppressed antitumor immunity and enhanced tumor expansion.


PLoS ONE ◽  
2016 ◽  
Vol 11 (8) ◽  
pp. e0160946 ◽  
Author(s):  
Vanja Bugarski-Stanojević ◽  
Gorana Stamenković ◽  
Jelena Blagojević ◽  
Thomas Liehr ◽  
Nadezda Kosyakova ◽  
...  

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5150-5150
Author(s):  
Caixia Li ◽  
De Pei Wu ◽  
Xue Guang Zhang

Abstract CXCR4, receptor of the chemokine stromal derived factor-1 (SDF-1), is expressed on CD34+ cells, and has been implicated in the process of CD34+ cell migration and homing. We studied the mobilization of CD34/CXCR4 cells and the plasma levels of SDF-1 and sgp130 in 22 patients, 11 acute Leukemia, 5 non-Hodgkin’s lymphoma, and 6 multiply myloma respectably, receiving cyclophosphamide (Cy) and plus G-CSF, or Mitoxantrone(Mit) and Cytarabine plus G-CSF for peripheral blood stem cell (PBSC) mobilization and autotransplantation. We observed lower plasma levels of SDF-1 in PBSCs compared with premobilized PB and bone marrow samples. The average levels of SDF-1 and sgp130 were 24.67±5.58ng/ml and 106.2±16.4ng/ml respectively while the level of SDF-1 as well as sgp130 decreased to 14659±2.11ng/ml(p&lt;0.05)and 58.8±29.1ng/ml(p&lt;0.05) respectively on day when PBSC was collected after mobilization. SDF-1 levels in the apheresis collections of the “good mobilizers” (patients who collected a minimum of 2 × 106 CD34+ cells/kg in one to three PBSC collections) were significantly lower than the apheresis collections of the “poor mobilizers” (&lt;2 × 106 CD34+ cells/kg in the three cycles of PBSC collections; 14.82 ± 7.08 ng/ml versus 27.2 ± 8.13 ng/ml; p&lt;0.01). The mean percentage of CD34+ cells expressing CXCR4 in the apheresis collections was decreased in the PBSC collections compared with premobilization values ranging from 32.09±5.39% to 22.4±5.92%. But the mean CXCR4 expression on CD34+ cells of the good mobilizers was not different from the expression on CD34+ cells of poor mobilizers. Furthermore, the levels of sgp130 closely correlated with SDF-1 levels (r = 0.87; p &lt; 0.001); the plasma level of SDF-1 and expression of CXCR4 on the CD34+ cells were gradually decreased in the PB of patients during the procession of mobilization; low plasma levels of SDF-1 turned out with good mobilization outcome, and the levels of SDF-1 correlated with sgp130, suggesting an association of these cytokines in mobilization of CD34+ cells.


Blood ◽  
1999 ◽  
Vol 94 (4) ◽  
pp. 1330-1336
Author(s):  
Mirian Lansink ◽  
Miek Jong ◽  
Martin Bijsterbosch ◽  
Marian Bekkers ◽  
Karin Toet ◽  
...  

Several clinical studies have demonstrated an inverse relationship between circulating levels of estrogen and tissue-type plasminogen activator (t-PA). The present study was designed to test the hypothesis that estrogens lower plasma levels of t-PA by increasing its clearance from the bloodstream. 17-Ethinyl estradiol (EE) treatment resulted in a significant increase in the clearance rate of recombinant human t-PA in mice (0.46 mL/min in treated mice v 0.32 mL/min in controls; P < .01). The clearance of endogenous, bradykinin-released t-PA in rats was also significantly increased after EE treatment (area under the curve [AUC], 24.9 ng/mL · min in treated animals v 31.9 ng/mL · min in controls; P < .05). Two distinct t-PA clearance systems exist in vivo: the low-density lipoprotein receptor-related protein (LRP) on liver parenchymal cells and the mannose receptor on mainly liver endothelial cells. Inhibition of LRP by intravenous injection of receptor-associated protein (RAP) as a recombinant fusion protein with Salmonella japonicum glutathione S-transferase (GST) significantly retarded t-PA clearance in control mice (from 0.41 to 0.25 mL/min; n = 5, P < .001) and EE-treated mice (from 0.66 to 0.35 mL/min; n = 5, P < .005), but did not eliminate the difference in clearance capacity between the 2 experimental groups. Similar results were obtained in mice in which LRP was inhibited via overexpression of the RAP gene in liver by adenoviral gene transduction. In contrast, administration of mannan, a mannose receptor antagonist, resulted in identical clearances (0.22 mL/min in controls and 0.24 mL/min in EE-treated mice). Northern blot analysis showed a 6-fold increase in mannose receptor mRNA expression in the nonparenchymal liver cells of EE-treated mice, whereas the parenchymal LRP mRNA levels remained unchanged. These findings were confirmed at the protein level by ligand blotting and Western blotting analysis. Our results demonstrate that EE treatment results in increased plasma clearance rate of t-PA via induction of the mannose receptor and could explain for the inverse relationship between estrogen status and plasma t-PA concentrations as observed in humans.


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