Vilon Peptide: Research Into Immune Cell Proliferation, Differentiation, and Regulation

Vilon peptide is also referred to as Lysylglutamic Acid or Lysylglutamate. Vilon is a dipeptide composed of amino acids lysine and glutamic acid. It falls into the category of bio-modulators similar to most other Khavinson’s peptides. It is thought to interact with various genetic structures and possibly modify gene expression related to immune cell regulation, proliferation, and differentiation. It continues to be experimented with in regard to its immunomodulatory potential in different settings, including laboratory models of lymphopenia, tumor cell formation, and others.⁽¹⁾

Fig1 – Vilon chemical structure⁽²⁾

 

Latest Research on Vilon Peptide

Vilon Mechanisms of Action

In vitro research by Lezhava et al. has explored the potential actions of Vilon on chromatin structures within cultured lymphocytes.⁽³⁾ As a reference, chromatin is composed of DNA and associated proteins and includes distinct functional domains: constitutive heterochromatin and facultative heterochromatin. Constitutive heterochromatin consists largely of non-coding satellite DNA located near centromeres, while facultative heterochromatin contains condensed euchromatic regions with genes that are not actively transcribed.

Lezhava et al. suggest that Vilon peptide may induce deheterochromatinization, or unrolling, of total heterochromatin. This process potentially reactivates ribosomal genes by decondensing nucleolus organizer regions (NORs), which are essential for ribosomal RNA synthesis. By reactivating these genes, Vilon might support synthetic processes within the cells. Additionally, Vilon appears to release genes that were repressed due to the condensation of euchromatic regions forming facultative heterochromatin.

This decondensation may allow previously inactive genes to become transcriptionally active, possibly influencing various cellular functions. Importantly, Vilon peptide does not seem to induce decondensation of pericentromeric structural heterochromatin, indicating that its actions may be selective toward facultative heterochromatin. This specificity suggests that “Vilon causes progressive activation (deheterochromatinization) of the facultative heterochromatin with increased aging” of the cells, as stated by the authors. This mechanism might be associated with its potential to activate or suppress different genes and consequently affect immune cell proliferation and differentiation.

Previous studies by Sevostianova et al. have also posited that short peptides like Vilon may regulate gene expression and stimulate thymocyte activation.⁽⁴⁾ For instance, Vilon has been associated with increased expression of markers such as HLA-DR and CD54 in thymic cell cultures. It may also normalize lymphocyte blast-transformation responses, which are considered to be crucial for proper immune function. These actions imply that Vilon peptide might modulate immune cell functions at the molecular level.

Vilon Peptide and Cellular Proliferation

Research by Khavinson et al. suggests that Vilon peptide may stimulate the proliferative activity of thymocytes, which are essential cells within the thymus involved in immune responses.⁽⁵⁾ In experimental models exposed to γ-irradiation, Vilon appeared to promote recovery in critical tissues. Histological analyses revealed that Vilon might lead to the enlargement of thymic lobules, primarily due to the widening of the cortical layer. There was an observed increase in the presence of proliferating cell nuclear antigen (PCNA)-positive nuclei within the thymus, which indicates heightened thymocyte proliferation. The proliferative index (I_PCNA) in the thymus increased from 26% to 37% with Vilon peptide exposure, suggesting well-supported cellular activity in this organ.

Vilon peptide was also studied by Ivanov et al. in an experimental model of low lymphocyte count due to repeated irradiation. In this experiment, Vilon appeared to normalize lymphocyte numbers, contrasting with the radioactive-chemical control group where lymphopenia persisted. Additionally, the Vilon group exhibited a higher number of granulocytes compared to the intact control group.⁽⁶⁾ Khavinson et al. suggest that this peptide possibly supports the proliferative potential of stem cells in the intestinal epithelium, particularly within the duodenal mucosa, indicating a role in supporting the regenerative processes of the gastrointestinal tract.⁽⁵⁾

Within the duodenal mucosa, Vilon exposure was associated with a 3.4% increase in the proliferative index in the crypt generation zones and a 1.5-fold increase in the number of cells entering mitosis. This support implies that Vilon may support the renewal and repair of the intestinal lining by stimulating stem cell activity. Moreover, Vilon was observed normalizing the histological appearance of intestinal crypts following exposure to radiation, which may indicate its potential role in facilitating tissue recovery.

Vilon Peptide and Lymphocyte Differentiation

Sevostianova et al. have also observed that Vilon may induce the differentiation of T-cell precursors toward CD4⁺ T-helper cells.⁽⁴⁾ Specifically, research suggests that Vilon may increase the expression of the lymphocyte differentiation marker CD5 in thymic cells. This increase in CD5 expression indicates that Vilon might play a role in promoting the differentiation of lymphocyte precursors. The influence of Vilon peptide on CD5 and CD4 expression suggests it might affect the early stages of T-cell development. This may mean that Vilon peptide facilitates the maturation process of thymic cells into functional T-helper cells.

Another experiment by Raikhlin et al. also investigated the potential actions of Vilon peptide on the expression of argyrophilic proteins within nucleolar organizer regions (NOR) of thymocytes and epithelial cells in co-culture systems.⁽⁷⁾ These argyrophilic proteins are posited as integral to the formation, assembly, and transport of ribosomes into the cytoplasm, thereby influencing the overall intensity of protein synthesis within cells. The study reported that when Vilon was introduced to cultures containing thymocytes and thymic epithelial cells, the peptide appeared to stimulate the expression of NOR-associated argyrophilic proteins in both cell types.

It is thought that increased concentrations of Vilon may correlate with a higher number of silver granules—markers indicative of argyrophilic protein expression—within the nuclei. This suggests a possible upregulation of ribosomal biogenesis and better-supported protein synthesis capacity. Moreover, Vilon possibly exhibited a direct mitogenic action on thymocytes. The researchers also stated that “a direct mitogenic effect of Vilon was also revealed: this peptide promoted thymocyte transformation into proliferating blast cells.” Such blast transformation is often associated with increased metabolic activity and heightened transcriptional activity of ribosomal RNA genes.

Vilon Peptide and Tumor Cell Occurrence

Khavinson et al. have also studied Vilon peptide and its potential actions in reducing the risk of tumor cell formation. Vilon-exposed models were reported as possibly exhibiting a lower incidence of pulmonary adenoma cells and mammary adenocarcinoma cells compared to controls.⁽⁸⁾ The underlying mechanisms are not fully understood, but it is posited that Vilon’s immunomodulatory properties might contribute to its actions on tumor cell inhibition. By potentially supporting immune system function, Vilon may help maintain cellular integrity and reduce the accumulation of age-related cellular damage.

In an experiment by Pliss et al., Vilon peptide appeared to decrease the occurrence of preneoplastic and early neoplastic changes in the urinary bladder mucosa twofold.⁽⁹⁾ The number of tumor cell nodes per animal was also lower in the Vilon group, averaging 1.5 cell nodes versus 2.6 cell nodes in the controls. Microscopic analysis indicated that Vilon might delay the formation of tumor cells in the urothelium. Overall, tumor cell formation was noted in 14.3% of the Vilon group compared to 29.7% in the control group. These observations imply that Vilon might potentially inhibit both the initiation stages of carcinogenesis and tumor cell occurrence. The mechanisms by which Vilon peptide exerts these actions may include stimulating the immune system, supporting tissue regeneration, and inhibiting inflammatory processes.

 
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References:

1. Kazakova TB, Barabanova SV, Khavinson VKh, Glushikhina MS, Parkhomenko EP, Malinin VV, Korneva EA. In vitro effect of short peptides on expression of interleukin-2 gene in splenocytes. Bull Exp Biol Med. 2002 Jun;133(6):614-6.
2. National Center for Biotechnology Information (2022). PubChem Compound Summary for CID 7010502, Lysylglutamic acid. Retrieved November 21, 2022 from https://pubchem.ncbi.nlm.nih.gov/compound/Lysylglutamic-acid
3. Lezhava T, Khavison V, Monaselidze J, Jokhadze T, Dvalishvili N, Bablishvili N, Barbakadze S. Bioregulator Vilon-induced reactivation of chromatin in cultured lymphocytes from old people. Biogerontology. 2004;5(2):73-9. doi: 10.1023/B:BGEN.0000025070.90330.7f. PMID: 15105581.
4. Sevostianova NN, Linkova NS, Polyakova VO, Chervyakova NA, Kostylev AV, Durnova AO, Kvetnoy IM, Abdulragimov RI, Khavinson VH. Immunomodulating effects of Vilon and its analogue in the culture of human and animal thymus cells. Bull Exp Biol Med. 2013 Feb;154(4):562-5. English, Russian. doi: 10.1007/s10517-013-2000-0. PMID: 23486604.
5. Khavinson VK, Kvetnoii IM. Peptide bioregulators inhibit apoptosis. Bull Exp Biol Med. 2000 Dec;130(12):1175-6. PMID: 11276315.
6. Ivanov SD, Khavinson VKh, Malinin VV, Kovan’ko EG, Iamshanov VA, Kondrat’eva AV, Morozov VG. [Vilon effect on consequences of repeated radioactive and mercuric impact in small doses]. Adv Gerontol. 2005;16:88-91. Russian. PMID: 16075682.
7. Raikhlin NT, Bukaeva IA, Smirnova EA, Yarilin AA, Sharova NI, Mitneva MM, Khavinson VKh, Polyakova VO, Trofimov AV, Kvetnoi IM. Expression of argyrophilic proteins in the nucleolar organizer regions of human thymocytes and thymic epitheliocytes under conditions of coculturing with vilon and epithalon peptides. Bull Exp Biol Med. 2004 Jun;137(6):588-91. doi: 10.1023/b:bebm.0000042720.40439.16. PMID: 15455093.
8. Khavinson VK, Anisimov VN, Zavarzina NY, Zabezhinskii MA, Zimina OA, Popovich IG, Shtylik AV, Malinin VV, Morozov VG. Effect of vilon on biological age and lifespan in mice. Bull Exp Biol Med. 2000 Jul;130(7):687-90. doi: 10.1007/BF02682106. PMID: 11140587.
9. Pliss GB, Mel’nikov AS, Malinin VV, Khavinson VK. Inhibitory effect of peptide vilon on the development of induced rat urinary bladder tumors in rats. Bull Exp Biol Med. 2001 Jun;131(6):558-60. doi: 10.1023/a:1012354603132. PMID: 11586406.