scholarly journals Trichuris muris whey acidic protein induces type 2 protective immunity against whipworm

2018 ◽  
Vol 14 (8) ◽  
pp. e1007273 ◽  
Author(s):  
Neima Briggs ◽  
Junfei Wei ◽  
Leroy Versteeg ◽  
Bin Zhan ◽  
Brian Keegan ◽  
...  
Endocrinology ◽  
2011 ◽  
Vol 152 (8) ◽  
pp. 3233-3245 ◽  
Author(s):  
Zhaoyu Sun ◽  
Sain Shushanov ◽  
Derek LeRoith ◽  
Teresa L. Wood

The IGFs and the IGF type 1 receptor (IGF-1R) are essential mediators of normal mammary gland development in mice. IGF-I and the IGF-1R have demonstrated functions in formation and proliferation of terminal end buds and in ductal outgrowth and branching during puberty. To study the functions of IGF-1R during pregnancy and lactation, we established transgenic mouse lines expressing a human dominant-negative kinase dead IGF-1R (dnhIGF-1R) under the control of the whey acidic protein promoter. We provide evidence that the IGF-1R pathway is necessary for normal epithelial proliferation and alveolar formation during pregnancy. Furthermore, we demonstrate that the whey acidic protein-dnhIGF-1R transgene causes a delay in alveolar differentiation including lipid droplet formation, lumen expansion, and β-casein protein expression. Analysis of IGF-1R signaling pathways showed a decrease in P-IGF-1R and P-Akt resulting from expression of the dnhIGF-1R. We further demonstrate that disruption of the IGF-1R decreases mammary epithelial cell expression of the signaling intermediates insulin receptor substrate (IRS)-1 and IRS-2. No alterations were observed in downstream signaling targets of prolactin and progesterone, suggesting that activation of the IGF-1R may directly regulate expression of IRS-1/2 during alveolar development and differentiation. These data show that IGF-1R signaling is necessary for normal alveolar proliferation and differentiation, in part, through induction of signaling intermediates that mediate alveolar development.


2005 ◽  
Vol 94 (2) ◽  
pp. 244-252 ◽  
Author(s):  
Marlena C. Kruger ◽  
Gabrielle G. Plimmer ◽  
Linda M. Schollum ◽  
Neill Haggarty ◽  
Satyendra Ram ◽  
...  

Bovine milk has been shown to contain bioactive components with bone-protective properties. Earlier studies on bovine milk whey protein showed that it suppressed bone resorption in the female ovariectomised rat. A new osteotropic component was subsequently identified in the whey basic protein fraction, but bone bioactivity may also be associated with other whey fractions. In the present study, we investigated whether acidic protein fractions isolated from bovine milk whey could prevent bone loss in mature ovariectomised female rats. Six-month-old female rats were ovariectomised (OVX) or left intact (sham). The OVX rats were randomised into four groups. One group remained the control (OVX), whereas three groups were fed various whey acidic protein fractions from milk whey as 3g/kg diet for 4 months. Outcomes were bone mineral density, bone biomechanics and markers of bone turnover. Bone mineral density of the femurs indicated that one of the whey AF over time caused a recovery of bone lost from OVX. Plasma C-telopeptide of type I collagen decreased significantly in all groups except OVX control over time, indicating an anti-resorptive effect of whey acidic protein. Biomechanical data showed that the AF may affect bone architecture as elasticity was increased by one of the whey AF. The femurs of AF-supplemented rats all showed an increase in organic matter. This is the first report of an acidic whey protein fraction isolated from milk whey that may support the recovery of bone loss in vivo.


Parasitology ◽  
1990 ◽  
Vol 100 (3) ◽  
pp. 479-489 ◽  
Author(s):  
K. J. Else ◽  
D. Wakelin

SUMMARYStrains of mice poorly (B10) or non-responsive (B10.BR) to a primary infection with Trichuris muris were protected against infection by vaccination with excretory/secretory (E/S) antigen in Complete Freund's Adjuvant (CFA). Protection in these mice was slow to be expressed compared to that in good responder strains. Vaccination boosted the IgG and IgG1 antibody responses to E/S antigen and altered the antigen recognition profiles, three high molecular weight antigens (80–85, 90–95, 105–110 kDa) being recognized by antibodies in sera from vaccinated but not control mice. B10. BR mice which had experienced a patent primary infection could not be protected against challenge infections by vaccination and this was correlated with depressed levels of IgG1, but not total IgG, to E'S antigen early post-challenge compared with vaccinated infected mice which had not seen an adult primary infection. There was also lack of recognition of the three high molecular weight antigens recognized by antibodies in sera from mice infected after vaccination. It is suggested that the rapid development of high levels of IgG1 antibodies, and the recognition of the three high molecular weight antigens, may reflect events that are important in protective immunity. Immunomodulation of host immunity by T. muris may therefore be achieved, at least in part, by the suppression of specific IgG1 levels, the production of an irrelevant IgG isotype and prevention of the recognition of critical antigens.


2013 ◽  
Vol 304 (10) ◽  
pp. R791-R798 ◽  
Author(s):  
Megan E. Probyn ◽  
Emma-Kate Lock ◽  
Stephen T. Anderson ◽  
Sarah Walton ◽  
John F. Bertram ◽  
...  

High levels of alcohol consumption during pregnancy can lead to growth deficits in early postnatal life. However, the effects of low-to-moderate alcohol consumption during pregnancy are less clearly defined. The aim of this study was to determine whether low-to-moderate ethanol (EtOH) consumption throughout pregnancy in the rat alters maternal mammary gland morphology and milk protein levels, thereby affecting lactation and the growth of pups after birth. Sprague-Dawley rats were fed an ad libitum liquid diet ± 6% vol/vol EtOH throughout pregnancy. Mammary glands from dams were collected at embryonic day (E) 20 or postnatal day (PN) 1, and expression of milk proteins (α-lactalbumin, β-casein, and whey acidic protein) was examined. In addition, relative amounts of alveoli, lactiferous ducts, adipose tissue, and blood vessels were determined at PN1. A subset of rats gave birth, and offspring growth and milk intake were recorded. Mammary gland weight was unaltered by EtOH, and stereological analysis showed no differences in gland structure compared with control. Although there were no significant changes in mammary gland gene expression at the RNA level, protein levels of α-lactalbumin were increased and whey acidic protein were decreased by EtOH. Offspring of EtOH-fed dams consumed less milk than controls in the lactational period; however, this did not alter their early postnatal growth. Overall, it appears that low-to-moderate-dose prenatal EtOH exposure does not significantly alter mammary gland development but may alter the composition of the various proteins found within the milk in a manner that maintains overall pup growth.


2006 ◽  
Vol 52 (2) ◽  
pp. 315-320 ◽  
Author(s):  
Naoko NUKUMI ◽  
Mami SEKI ◽  
Tokuko IWAMORI ◽  
Tetsushi YADA ◽  
Kunihiko NAITO ◽  
...  

2005 ◽  
Vol 51 (5) ◽  
pp. 649-656 ◽  
Author(s):  
Naoko NUKUMI ◽  
Tokuko IWAMORI ◽  
Kunihiko NAITO ◽  
Hideaki TOJO

2001 ◽  
Vol 359 (3) ◽  
pp. 557-565 ◽  
Author(s):  
Benjamin MILLOT ◽  
Marie-Louise FONTAINE ◽  
Dominique THEPOT ◽  
Eve DEVINOY

The aim of the present study was to identify the functional domains of the upstream region of the rabbit whey acidic protein (WAP) gene, which has been used with considerable efficacy to target the expression of several foreign genes to the mammary gland. We have shown that this region exhibits three sites hypersensitive to DNase I digestion in the lactating mammary gland, and that all three sites harbour elements which can bind to Stat5 in vitro in bandshift assays. However, not all hypersensitive regions are detected at all stages from pregnancy to weaning, and the level of activated Stat5 detected in the rabbit mammary gland is low except during lactation. We have studied the role of the distal site, which is only detected during lactation, in further detail. It is located within a 849bp region that is required to induce a strong expression of the chloramphenicol acetyltransferase reporter gene in transfected mammary cells. Taken together, these results suggest that this region, centred around a Stat5-binding site and surrounded by a variable chromatin structure during the pregnancy–lactation cycle, may play a key role in regulating the expression of this gene in vivo. Furthermore, this distal region exhibits sequence similarity with a region located around 3kb upstream of the mouse WAP gene. The existence of such a distal region in the mouse WAP gene may explain the differences in expression between 4.1 and 2.1kb mouse WAP constructs.


1990 ◽  
Vol 18 (12) ◽  
pp. 3641-3641 ◽  
Author(s):  
D. Thepot ◽  
E. Devinoy ◽  
M.L. Fontaine ◽  
C. Hubert ◽  
L.M. Houdebine

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