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Yolkin, an egg yolk immunoregulatory protein, stimulates the humoral but inhibits the cellular immune response in adult mice. The aim of this investigation was to evaluate the effects of yolkin administration on the immune response using a model of juvenile, i.e., 28-day- and 37-day-old, mice. We examined the yolkin influence on the magnitude of the cellular immune response, which was determined as contact sensitivity (CS) to oxazolone (OXA), and the humoral immune response, which was determined as the antibody response to ovalbumin (OVA). Yolkin was administered in drinking water, followed by immunization with OXA or OVA. In parallel, the phenotypic changes in the lymphoid organs were determined following yolkin treatment and prior immunization. The results showed that yolkin had a stimulatory effect on CS in the mice treated with yolkin from the 37th day of life but not from the 28th day of life. In contrast, no regulatory effect of yolkin on antibody production was found in 28-day- and 37-day-old mice. Phenotypic studies revealed significant changes in the content of B cells and T cell subpopulations, including CD4+CD25+Foxp3 regulatory T cells. The association between the effects of yolkin on the magnitude of CS and phenotypic changes in main T- and B-cell compartments, as well the importance of changes in T-regulatory and CD8+ cells in the age categories, are discussed. We conclude that the immunoregulatory effects of yolkin on the generation of CS in mice are age dependent and change from stimulation in juvenile to suppression in adult mice. [ABSTRACT FROM AUTHOR]

Yolkin, an egg yolk immunoregulatory protein, stimulates the humoral but inhibits the cellular immune response in adult mice. The aim of this investigation was to evaluate the effects of yolkin administration on the immune response using a model of juvenile, i.e., 28-day- and 37-day-old, mice. We examined the yolkin influence on the magnitude of the cellular immune response, which was determined as contact sensitivity (CS) to oxazolone (OXA), and the humoral immune response, which was determined as the antibody response to ovalbumin (OVA). Yolkin was administered in drinking water, followed by immunization with OXA or OVA. In parallel, the phenotypic changes in the lymphoid organs were determined following yolkin treatment and prior immunization. The results showed that yolkin had a stimulatory effect on CS in the mice treated with yolkin from the 37th day of life but not from the 28th day of life. In contrast, no regulatory effect of yolkin on antibody production was found in 28-day- and 37-day-old mice. Phenotypic studies revealed significant changes in the content of B cells and T cell subpopulations, including CD4+CD25+Foxp3 regulatory T cells. The association between the effects of yolkin on the magnitude of CS and phenotypic changes in main T- and B-cell compartments, as well the importance of changes in T-regulatory and CD8+ cells in the age categories, are discussed. We conclude that the immunoregulatory effects of yolkin on the generation of CS in mice are age dependent and change from stimulation in juvenile to suppression in adult mice.

Yolkin is a polypeptide complex isolated from hen egg yolk that exhibits immunomodulating properties. The aim of the present study was to determine whether in-ovo-delivered yolkin affects leukocyte populations and cytokine levels in broiler chickens. The experiment was carried out on eggs from Ross 308 broiler breeder birds. Yolkin was administered in ovo on the 18th day of incubation, once, at the following three doses: 1, 10, or 100 µg/egg. The immunological parameters were assessed in 1-, 7-, 14-, 21-, 28-, 35-, and 42-day-old birds kept under farming conditions and routinely vaccinated. The leukocyte populations were determined in the thymus, spleen, and blood. The cytokine (IL-1β, IL-2, IL-6, and IL-10) levels were determined in the plasma of the broiler chickens. Each experimental group included eight birds. The most pronounced effect of yolkin was an increase in the population of T cells, both CD4+ and CD8+, mainly in the blood. This effect on the lymphocyte subsets may be valuable regarding chicken immune responses, mainly against T-dependent antigens, during infection or after vaccination. [ABSTRACT FROM AUTHOR]

Food-derived bioactive peptides able to regulate neuronal function have been intensively searched and studied for their potential therapeutic application. Our previous study showed that a polypeptide complex yolkin, isolated from hen egg yolk as a fraction accompanying immunoglobulin Y (IgY), improved memory and cognitive functions in rats. However, the mechanism activated by the yolkin is not explained. The goal of the present study was to examine what molecular mechanism regulating brain-derived neurotrophic factor (BDNF) expression is activated by the yolkin complex, using in vitro models of PC12 cell line and fetal rat hippocampal cell line H19-7. It was shown that yolkin increased the proliferative activity of rat hippocampal precursor cells H19-7 cells and upregulated the expression/production of BDNF in a cyclic adenosine monophosphate (cAMP)-response element-binding protein (CREB)-dependent manner. Additionally the upregulation of carboxypeptidase E/neurotrophic factor–α1 (CPE/(NF-α1) expression was shown. It was also determined that upregulation of CREB phosphorylation by yolkin is dependent on cyclic adenosine monophosphate/protein kinase A (cAMP/PKA) and phosphoinositide 3-kinases/protein kinase B (PI3K/Akt) signaling pathway activation. Moreover, the impact of yolkin on the level of intracellular Ca2+, nitric oxide, and activation of extracellular signal-regulated kinases 1/2 (ERK 1/2 kinase) was excluded. These results emphasize that yolkin can act comprehensively and in many directions and may participate in the regulation of neurons' survival and activity. Therefore, it seems that the yolkin specimen can be used in the future as a safe, bioavailable, natural nutraceutical helping to improve the cognition of older people. [ABSTRACT FROM AUTHOR]

ABSTRACT: Vitellogenin (Vt) is considered the primary protein precursor of egg yolk, serving as a source of protein- and lipid-rich nutrients for the developing embryo. However, recent research has revealed that the functions of Vt and Vt-derived polypeptides, such as yolkin (Y) and yolk glycopeptide 40 (YGP40), extend beyond their nutritional roles as a source of amino acids. Emerging evidence has demonstrated that both Y and YGP40 possess immunomodulatory properties and can contribute to host immune defenses. Additionally, Y polypeptides have been shown to exhibit neuroprotective activity, participating in the modulation of neurons’ survival and activity, inhibiting neurodegeneration processes, and improving cognitive functions in rats. These non-nutritional functions not only enhance our understanding of the physiological roles of these molecules during embryonic development but also offer a promising basis for the potential application of these proteins in human health.

Ageing is accompanied by the inevitable changes in the function of the immune system. It provides increased susceptibility to chronic infections that have a negative impact on the quality of life of older people. Therefore, rejuvenating the aged immunity has become an important research and therapeutic goal. Yolkin, a polypeptide complex isolated from hen egg yolks, possesses immunoregulatory and neuroprotective activity. Considering that macrophages play a key role in pathogen recognition and antigen presentation, we evaluated the impact of yolkin on the phenotype and function of mouse bone marrow-derived macrophages of the BMDM cell line. We determined yolkin bioavailability and the surface co-expression of CD80/CD86 using flow cytometry and IL-6, IL-10, TGF-β and iNOS mRNA expression via real-time PCR. Additionally, the impact of yolkin on the regulation of cytokine expression by MAPK and PI3K/Akt kinases was determined. The stimulation of cells with yolkin induced significant changes in cell morphology and an increase in CD80/CD86 expression. Using pharmaceutical inhibitors of ERK, JNK and PI3K/Akt, we have shown that yolkin is able to activate these kinases to control cytokine mRNA expression. Our results suggest that yolkin is a good regulator of macrophage activity, priming mainly the M1 phenotype. Therefore, it is believed that yolkin possesses significant therapeutic potential and represents a promising possibility for the development of novel immunomodulatory medicine. [ABSTRACT FROM AUTHOR]

• Yolkin is a protein from egg's yolk. • Yolkin stimulates the humoral immune response in mice. • Yolkin provides differentiation signals for Jurkat and WEHI 231 cells. • Yolkin significantly increases B cell content in lymphoid organs. • Yolkin may promote immune system maturation in birds. Yolkin is a product of proteolytic degradation of vitellogenin, a protein contained in eggs' yolk, with already described procognitive properties. Here, we investigated effects of yolkin on the humoral and cellular immune response in mice, phenotype of cells from lymphoid organs and function of innate immunity cells. In vitro studies included effects of yolkin on mitogen-induced thymocyte proliferation, percentage of CD19 cells in bone marrow cells culture, expression of signaling molecules in Jurkat cells, interleukin 2 receptor (IL-2R) subunits in WEHI 231 cells and susceptibility of these cells to anti-Ig-induced cell death. The results showed that repeatable i.p. injections of yolkin stimulated the humoral immune response to sheep red blood cells (SRBC) irrespective of the time of the treatment. On the other hand, yolkin inhibited contact sensitivity to oxazolone. Treatment of mice with yolkin diminished the percentage of double positive cells and increasing the content of single positive CD4+ and CD8+ cells in the thymus. At the same time an increase of percentage of CD19 + B cells in the spleen and mesenteric lymph nodes was observed. In addition, the protein, given i.p., diminished ex vivo ability to synthesize nitric oxide by resident, peritoneal macrophages, stimulated with lipopolisaccharide (LPS). In vitro studies showed that yolkin increased CD19+ cell content in bone marrow cell population. The protein also enhanced proliferation of thymocytes to concanavalin A and stimulated expression of MAP kinases in Jurkat cells. In WEHI 231 B cell line yolkin caused a loss of IL-2R gamma chain expression, correlated with an increased resistance of these cells to proapoptotic action of anti-Ig antibodies. In conclusion, this is a first demonstration of immunotropic properties of yolkin in in vitro and in vivo tests. The results provide evidence for induction of maturation and stimulatory signals in immature T and B cells by the protein, suggesting its potential role in the development of an embryo's immune system. [ABSTRACT FROM AUTHOR]

Substances isolated from natural sources showing a character of endogenous regulators may have a circular meaning. One example is yolkin, which can be useful as a natural therapeutic agent for treating immunological disorders. In the present work we studied the effect of degree of deglycosylation on the biological activity of yolkin polypeptides. For this purpose, yolkin from hen egg yolk was fractionated by gel permeation chromatography (Sephacryl S 100 - HR and Zorbax GF- 250 columns) and enzymatically deglycosylated. The immunoregulatory activity of yolkin fractions (ysec, y4 and y9) were estimated by their induction of proinflammatory factors. The induction of cytokines IL-6, IL-10, and TNF-α in human whole blood cell cultures and nitric oxide from bone-marrow mouse macrophages BMDM were measured. The obtained results showed that all of the yolkin polypeptides, irrespective of size, exerted a strong cytokine and nitric oxide induction, indicating that all of the yolkin constituents possess these activities. The results indicated that the presence of carbohydrate in yolkin polypeptides is unnecessary to preserve cytokine inducing activity and NO generation. Furthermore the removal of carbohydrates from the yolkin by PNGase F led to a significant increase in the level of secretion of nitric oxide from the macrophages. [ABSTRACT FROM AUTHOR]

Vitellogenin (Vt) is considered the primary protein precursor of egg yolk, serving as a source of protein- and lipid-rich nutrients for the developing embryo. However, recent research has revealed that the functions of Vt and Vt-derived polypeptides, such as yolkin (Y) and yolk glycopeptide 40 (YGP40), extend beyond their nutritional roles as a source of amino acids. Emerging evidence has demonstrated that both Y and YGP40 possess immunomodulatory properties and can contribute to host immune defenses. Additionally, Y polypeptides have been shown to exhibit neuroprotective activity, participating in the modulation of neurons' survival and activity, inhibiting neurodegeneration processes, and improving cognitive functions in rats. These non-nutritional functions not only enhance our understanding of the physiological roles of these molecules during embryonic development but also offer a promising basis for the potential application of these proteins in human health. [ABSTRACT FROM AUTHOR]

A large number of bioactive peptides isolated from natural sources are known to play important physiological roles in the human body. It is possible to use these as alternative therapy agents. One example is yolkin which can be useful as a food supplement, a natural therapeutic agent for preventing and treating cognitive disorders of various origins, preferably in patients with unsatisfactory responses to known therapies. A new simple method of isolation of yolkin based on precipitation with ethanol or acetone was developed. The best precipitation efficiency of both ethanol and acetone was achieved when stirred into the starting material to a final concentration of 70%. These methods preserved the ability of yolkin to stimulate human whole blood cells to release anti-inflammatory cytokines and neurotrophins. At first we indicated that yolkin displayed a potential neuroprotective effect by the ability to stimulate cells to produce pro-survival brain derived neurotrophic factor (BDNF). [ABSTRACT FROM AUTHOR]

The protein mixture of cytokine-inducing activity accompanying chicken immunoglobulin Y, named yolkin, consists of several peptides of molecular weight (MW) ranging from over 1 to 35 kDa. Yolkin and its constituent peptides were found to be efficient inducers of interleukin (IL)-1β, IL-6 and IL-10 secretion. N-terminal amino acid sequences of eight of the electrophoretically purified yolkin constituents revealed that all of them are homological to some fragments of the C-terminal domain of vitellogenin II. The fractions of MW about 4 and 12 kDa are free of carbohydrates and start at position 1732 in the vitellogenin amino acid sequence; whereas the other fractions (MW about 16, 19, 23, 29, 32 and 35 kDa) appeared to be glycoproteins corresponding to the amino acid sequence of vitellogenin starting at position 1572. From these data, it is concluded that yolkin most likely represents vitellogenin-derived peptides that possess cytokine-inducing activity and are, at least partially, responsible for such properties of separated immunoglobulin Y preparation. This finding reveals a new role for vitellogenin as a reservoir of polypeptides that may play an important role in the innate immune system of the developing embryo. [ABSTRACT FROM AUTHOR]

The results of our research have proven that yolkin preparations isolated from eggs of different bird species show a high similarity in polypeptide composition. Despite the small differences in protein patterns, all of yolkin preparations showed also strong immunomodulatory activity, comparable with yolkin obtained previously from hen egg yolk. It can therefore be deducted that the presence of this polypeptide complex in the egg is not accidental and performs an important biological function for developing embryo., (© 2021 The Authors. Chemistry & Biodiversity published by Wiley-VHCA AG, Zurich, Switzerland.)