Enhancement of Human T Lymphocyte Function by Prothymosin α: Incremed Production of Interleukin-2 and Expression of Interleukin-2 Receptors in Normal Human Peripheral Blood t Lymphocytes

Baxevanis, Constantin N.; Frillingos, Stathis; Seferiadis, K.; Reclos, George J.; Arsenis, Paula; Katsiyiannis, Anna; Anastasopoulos, Emmanuel; Tsolas, Orestes; Papamichail, Michail

doi:10.3109/08923979009019679

Cited by 29 publications

(15 citation statements)

References 41 publications

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“…Numerous in vitro studies further confirmed the extracellular role of the polypeptide. As already aforementioned, peripheral blood T cells stimulated with proTα produced high amounts of IL-2 and increased the expression of IL-2 receptor on their surface (Baxevanis et al, 1990;Cordero et al, 1991), while APCs and DCs activated with proTα upregulated MHC class II and costimulatory molecules (CD11b, CD80, CD83, CD86, and CD40; Skopeliti et al, 2009), respectively. NK and LAK cells cultured in the presence of proTα augmented their cytotoxicity (Cordero, Sarandeses, López, & Nogueira, 1992;López-Rodríguez et al, 1994), and proTα-activated neutrophils showed increased chemotaxis, produced high amounts of ROS, and became cytotoxic against cancer cell targets (Heidecke, Eckert, Schulze-Forster, & Maurer, 1997;.…”

Section: The Extracellular Role Of Protαmentioning

confidence: 52%

Prothymosin Alpha and Immune Responses

Samara

Ioannou

Tsitsilonis

2016

Vitamins and Hormones

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The thymus gland produces soluble molecules, which mediate significant immune functions. The first biologically active thymic extract was thymosin fraction V, the fractionation of which led to the isolation of a series of immunoactive polypeptides, including prothymosin alpha (proTα). ProTα displays a dual role, intracellularly as a survival and proliferation mediator and extracellularly as a biological response modifier. Accordingly, inside the cell, proTα is implicated in crucial intracellular circuits and may serve as a surrogate tumor biomarker, but when found outside the cell, it could be used as a therapeutic agent for treating immune system deficiencies. In fact, proTα possesses pleiotropic adjuvant activity and a series of immunomodulatory effects (eg, anticancer, antiviral, neuroprotective, cardioprotective). Moreover, several reports suggest that the variable activity of proTα might be exerted through different parts of the molecule. We first reported that the main immunoactive region of proTα is the carboxy-terminal decapeptide proTα(100-109). In conjunction with data from others, we also revealed that proTα and proTα(100-109) signal through Toll-like receptor 4. Although their precise molecular mechanism of action is yet not fully elucidated, proTα and proTα(100-109) are viewed as candidate adjuvants for cancer immunotherapy. Here, we present a historical overview on the discovery and isolation of thymosins with emphasis on proTα and data on some immune-related new activities of the polypeptide and smaller immunostimulatory peptides thereof. Finally, we propose a compiled scenario on proTα's mode of action, which could eventually contribute to its clinical application.

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Section: The Extracellular Role Of Protαmentioning

confidence: 52%

Prothymosin Alpha and Immune Responses

Samara

Ioannou

Tsitsilonis

2016

Vitamins and Hormones

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“…PTMS likely mediates immune function by blocking the effects of prothymosin alpha (50), and reduces the production of IL-2 and IL-2R (IL-2 receptor) required for proliferation of CD4+ T cells (51, 52). As a pro-inflammatory cytokine, IL-2 stimulates lymphocytes, monocytes, lymphokine-activated killer cells, and natural killer cells critical to immune function (53).…”

Section: 4 Discussionmentioning

confidence: 99%

A standardized randomized 6-month aerobic exercise-training down-regulated pro-inflammatory genes, but up-regulated anti-inflammatory, neuron survival and axon growth-related genes

Iyalomhe

Chen

Allard

et al. 2015

Experimental Gerontology

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There is considerable support for the view that aerobic exercise may confer cognitive benefits to mild cognitively impaired elderly persons. However, the biological mechanisms mediating these effects are not entirely clear. As a preliminary step towards informing this gap in knowledge, we enrolled older adults confirmed to have mild cognitive impairment (MCI) in a 6-month exercise program. Male and female subjects were randomized into a 6-month program of either aerobic or stretch (control) exercise. Data collected from the first 10 completers, aerobic exercise (n=5) or stretch (control) exercise (n=5), were used to determine intervention-induced changes in the global gene expression profiles of the aerobic and stretch groups. Using microarray, we identified genes with altered expression (relative to baseline values) in response to the 6-month exercise intervention. Genes whose expression were altered by at least two-fold, and met the p-value cutoff of 0.01 were inputted into the Ingenuity Pathway Knowledge Base library to generate gene-interaction networks. After a 6-month aerobic exercise-training, genes promoting inflammation became down-regulated, whereas genes having anti-inflammatory properties and those modulating immune function or promoting neuron survival and axon growth, became up-regulated (all fold change ≥ ± 2.0, p < 0.01). These changes were not observed in the stretch group. Importantly, the differences in the expression profiles correlated with significant improvement in maximal oxygen uptake (VO2max) in the aerobic program as opposed to the stretch group. We conclude that three distinct cellular pathways may collectively influence the training effects of aerobic exercise in MCI subjects. We plan to confirm these effects using rt-PCR and correlate such changes with the cognitive phenotype.

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“…The initial observations came from in vivo studies in animals, where proT was able to protect immunosuppressed mice against infections caused by Candida albicans and other opportunistic infections [30]. When added in lymphocyte cultures, proT enhanced antigen or mitogen-induced T cell proliferation, increased the production of interleukin (IL)-2 and the expression (both in number and in density) of its receptor on T cells [31,32] and upregulated major histocompatibility complex (MHC) class II antigen expression on human monocytes [33]. ProT was also shown to stimulate the cytotoxicity of natural killer (NK) cells [34] and the induction of lymphokine-activated killer (LAK) cells activity [35].…”

Section: The Dual-intracellular and Extracellular-role Of Protmentioning

confidence: 99%

Prothymosin alpha: a ubiquitous polypeptide with potential use in cancer diagnosis and therapy

Ioannou

Samara

Livaniou

et al. 2012

Cancer Immunol Immunother

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The thymus is a central lymphoid organ with crucial role in generating T cells and maintaining homeostasis of the immune system. More than 30 peptides, initially referred to as "thymic hormones," are produced by this gland. Although the majority of them have not been proven to be thymus-specific, thymic peptides comprise an effective group of regulators, mediating important immune functions. Thymosin fraction five (TFV) was the first thymic extract shown to stimulate lymphocyte proliferation and differentiation. Subsequent fractionation of TFV led to the isolation and characterization of a series of immunoactive peptides/polypeptides, members of the thymosin family. Extensive research on prothymosin α (proTα) and thymosin α1 (Tα1) showed that they are of clinical significance and potential medical use. They may serve as molecular markers for cancer prognosis and/or as therapeutic agents for treating immunodeficiencies, autoimmune diseases and malignancies. Although the molecular mechanisms underlying their effect are yet not fully elucidated, proTα and Tα1 could be considered as candidates for cancer immunotherapy. In this review, we will focus in principle on the eventual clinical utility of proTα, both as a tumor biomarker and in triggering anticancer immune responses. Considering the experience acquired via the use of Tα1 to treat cancer patients, we will also discuss potential approaches for the future introduction of proTα into the clinical setting.

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Enhancement of Human T Lymphocyte Function by Prothymosin α: Incremed Production of Interleukin-2 and Expression of Interleukin-2 Receptors in Normal Human Peripheral Blood t Lymphocytes

Cited by 29 publications

References 41 publications

Prothymosin Alpha and Immune Responses

Prothymosin Alpha and Immune Responses

A standardized randomized 6-month aerobic exercise-training down-regulated pro-inflammatory genes, but up-regulated anti-inflammatory, neuron survival and axon growth-related genes

Prothymosin alpha: a ubiquitous polypeptide with potential use in cancer diagnosis and therapy

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