Thymic peptides restrain the inflammatory response in mice with experimental autoimmune encephalomyelitis

Лунин, С. М.; Глушкова, О. В.; Хренов, М. О.; Новоселова, Т. В.; Parfenyuk, Svetlana B.; Фесенко, Е. Е.; Новоселова, Е. Г.

doi:10.1016/j.imbio.2012.05.023

Cited by 19 publications

(13 citation statements)

References 30 publications

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“…Note that other panel of cytokines was tested in these experiments based on our previous data on thymulin activity. Indeed, these cytokines are predisposed to thymulin control [19]. …”

Section: Resultsmentioning

confidence: 99%

“…Additionally, it has been shown recently that thymulin significantly reduces the disease severity in mice with acute experimental autoimmune encephalomyelitis [33]. IL-17 and IL-6 are important in many disorders characterised by immune self-recognition, and IL-6 is known to induce the differentiation of Th17 cells [19, 34], but the role of Th17 cells in septic inflammation is still unclear. We demonstrated that the separate administration of the inhibitor and thymulin or their combination did not significantly change the plasma IL-17 concentration.…”

Section: Discussionmentioning

confidence: 99%

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Anti-Inflammatory Effects of IKK Inhibitor XII, Thymulin, and Fat-Soluble Antioxidants in LPS-Treated Mice

Новоселова

Хренов

Глушкова

et al. 2014

Mediators of Inflammation

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The present study was designed to compare the anti-inflammatory effects of several agents applied in vivo, namely, a synthetic inhibitor of the NF-κB cascade, fat-soluble antioxidants, and the thymic peptide thymulin. Cytokine response in LPS-treated mice was analysed in tandem with the following parameters: the synthesis of inducible forms of the heat shock proteins HSP72 and HSP90α; activity of the NF-κB and SAPK/JNK signalling pathways; and TLR4 expression. Inflammation-bearing Balb/c male mice were pretreated with an inhibitor of IKK-α/β kinases (IKK Inhibitor XII); with thymulin; with dietary coenzyme Q9, α-tocopherol, and β-carotene; or with combinations of the inhibitor and peptide or antioxidants. Comparable anti-inflammatory effects were observed in inflammation-bearing mice treated separately with thymulin or with dietary antioxidants administered daily for two weeks before LPS treatment. When LPS-injected mice were treated with the inhibitor and antioxidants together, neither plasma cytokines, signal proteins, nor heat shock proteins recovered more efficiently than when mice were treated with these agents separately. In contrast to antioxidant diet, the thymulin was shown to increase the effect of IKK Inhibitor XII in preventing IKK activation in LPS-treated mice.

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“…Note that other panel of cytokines was tested in these experiments based on our previous data on thymulin activity. Indeed, these cytokines are predisposed to thymulin control [19]. …”

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Anti-Inflammatory Effects of IKK Inhibitor XII, Thymulin, and Fat-Soluble Antioxidants in LPS-Treated Mice

Новоселова

Хренов

Глушкова

et al. 2014

Mediators of Inflammation

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“…In a recent report, Lunin et al studied the modulation of inflammation by thymulin in New Zealand White (NZW) mice with acute autoimmune encephalomyelitis, induced by myelin basic protein [73]. In this model, it was suggested that thymulin treatment reduced the severity of the desease and the autoimmune response via mechanisms involving the nuclear factor-kappaB (NF-9B) cascade.…”

Section: Analgesic and Antiinflammatory Actions Of Thymulin And Its Amentioning

confidence: 99%

Physiology and Therapeutic Potential of the Thymic Peptide Thymulin

Reggiani¹,

Schwerdt²,

Cónsole³

et al. 2014

CPD

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Thymulin is a thymic hormone exclusively produced by the epithelial cells of the thymus. After its discovery and initial characterization in the '70s, it was demonstrated that the production and secretion of thymulin are strongly influenced by the neuro-endocrine system. Conversely, a growing body of evidence, to be reviewed here, suggests that thymulin is a hypophysiotropic peptide. Additionally, a substantial body of information pointing to thymulin and a synthetic analog as anti-inflammatory and analgesic peptides in the central nervous system brain and other organs will be also reviewed. In recent years, a synthetic DNA sequence encoding a biologically active analog of thymulin, metFTS, was constructed and cloned in a number of adenovectors. These include bidirectional regulatable Tet-Off vector systems that simultaneously express metFTS and green fluorescent protein and that can be down-regulated reversibly by the addition of the antibiotic doxycycline. A number of recent studies indicate that gene therapy for thymulin may be an effective therapeutic strategy to prevent some of the hormonal and reproductive abnormalities that typically appear in congenitally athymic (nude) mice, used as a suitable model of neuroendocrine and reproductive aging. Summing up, this article briefly reviews the publications on the physiology of the thymulin-neuroendocrine axis and the anti-inflammatory properties of the molecule and its analog. The availability of novel biotechnological tools should boost basic studies on the molecular biology of thymulin and should also allow an assessment of the potential of gene therapy to restore circulating thymulin levels in thymodeficient animal models and eventually, in humans.

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“…This is in line with our earlier data that thymulin effects are mediated by NF-kappaB pathway. 5 , 21 However, changes in content of the 10 kDa intermediate were consistent with the caspase-3 activation and necrosis rather than the NF-kappaB activation, indicating the role of the intermediate in the pathological processes. Thus, the potential thymulin precursor is a stress-related protein being cleaved in some stress-related or pathological conditions and released into extracellular space.…”

Section: Discussionmentioning

confidence: 88%

Extrathymic production of thymulin induced by oxidative stress, heat shock, apoptosis, or necrosis

Лунин

Хренов

Глушкова

et al. 2017

Int J Immunopathol Pharmacol

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Thymic peptides are immune regulators produced mainly in the thymus. However, thymic peptides such as thymosin-α and thymopoietin have precursors widely expressed outside the thymus, localized in cell nuclei, and involved in vital nuclear functions. In stress-related conditions, they can relocalize. We hypothesized that another thymic peptide, thymulin, could be similarly produced by non-thymic cells during stress and have a precursor therein. Non-thymic cells, including macrophages and fibroblasts, were exposed to oxidative stress, heat, apoptosis, or necrosis. Extracellular thymulin was identified in media of both cell types 2 h after exposure to stress or lethal signals. Therefore, thymulin is released by non-thymic cells. To examine possible thymulin precursors in non-thymic cells, macrophage lysates were analyzed by western blotting. Bands stained with anti-thymulin antibody were detected in two locations, approximately 60 kDa and 10 kDa, which may be a possible precursor and intermediate. All of the exposures except for heat were effective for induction of the 10 kDa protein. BLAST search using thymulin sequence identified SPATS2L, an intranucleolar stress-response protein with molecular weight of 62 kDa, containing thymulin-like sequence. Comparisons of blots stained with anti-thymulin and anti-SPATS2L antibodies indicate that SPATS2L may be a possible candidate for the precursor of thymulin.

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Thymic peptides restrain the inflammatory response in mice with experimental autoimmune encephalomyelitis

Cited by 19 publications

References 30 publications

Anti-Inflammatory Effects of IKK Inhibitor XII, Thymulin, and Fat-Soluble Antioxidants in LPS-Treated Mice

Anti-Inflammatory Effects of IKK Inhibitor XII, Thymulin, and Fat-Soluble Antioxidants in LPS-Treated Mice

Physiology and Therapeutic Potential of the Thymic Peptide Thymulin

Extrathymic production of thymulin induced by oxidative stress, heat shock, apoptosis, or necrosis

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