Transforming growth factor β (TGF-β) pathway in the immunopathogenesis of multiple sclerosis (MS); molecular approaches

Esmaeilzadeh, Abdolreza; Mohammadi, V.; Elahi, Reza

doi:10.1007/s11033-023-08419-z

Cited by 5 publications

(4 citation statements)

References 125 publications

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“…During both phases, significantly lower levels of IFN-γ, IL10, IFN-γ, and significantly higher levels of TGF-β were reported in remission compared to the controls. Other observations report high values of TGF-β, IFN-γ, TNFα, and IL6 before exacerbation and compensatory over-activity is discussed [ 17 - 19 ]. During the two periods, significant differences were reported between the levels of certain cytokines: increase in IFN-γ during exacerbation and increase in IL4, TGF-β during remission.…”

Section: Discussionmentioning

confidence: 99%

25 Hydroxyvitamin D and Cytokine Profile in Patients With Relapsing-Remitting Multiple Sclerosis

Slavov,

Manova,

Kostadinova

2024

Cureus

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In experimental allergic encephalomyelitis, the severity of the deficiency is associated with the loss of axons, and it is likely that cytotoxic T-cells 8 (CD8 T) play an important role. In relapsing-remitting multiple sclerosis, there is a correlation between the inflammatory activity in the lesion and the transection of axons. To understand the pathological mechanisms, it is important to evaluate the changes in serum concentrations of pro-and anti-inflammatory cytokines during the disease course. A total of 46 patients and 40 healthy individuals participated in an open-label, prospective, case-control study from 2012 to 2014. The serum concentrations of cytokines were measured using enzyme-linked immunosorbent assay (ELISA). An immune imbalance was observed during relapse and remission phases compared to the control group. During relapse, the levels of interferon-gamma (IFN-γ) were significantly higher compared to those in remission (p=0.017). During remission, there was an improvement in the deficiency (p<0.001), and the antiinflammatory cytokines transforming growth factor-beta (TGF-β) and interleukin 4 (IL4) increased compared to those in relapse (p=0.006; p=0.009). A correlation was found between the serum concentrations of tumor necrosis factor-alpha (TNF-α) and Expanded Disability Status Scale (EDSS) during relapse (correlation coefficient: 0.301; significance (Sig.) (2-tailed 0.042). During the exacerbation, there was a moderate relationship between interleukin 17 (IL17) and 25-hydroxyvitamin D (25(OH)D) (P (p-value (probability value) = 0.02)). TNF-α, IFN-γ, IL17, and TGF-β serum levels are criteria for evaluating immune inflammatory activity during relapse and remission periods.

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Section: Discussionmentioning

confidence: 99%

25 Hydroxyvitamin D and Cytokine Profile in Patients With Relapsing-Remitting Multiple Sclerosis

Slavov,

Manova,

Kostadinova

2024

Cureus

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“…In addition to the function of TGF-β in cellular development, different members of the TGF-β superfamily are intensely studied for their widespread role in various diseases, including cancer [ 29 , 30 ]. TGF-β is known to strongly inhibit the proliferation of many cell types, including endothelial, epithelial, and immune cells, while playing a prominent role in controlling the differentiation of cell lineages during development [ 29 , 31 , 32 ]. Additionally, TGF-β family proteins are involved in other cellular functions such as promoting/protecting against cell death, cell motility, and invasion [ 29 , 31 , 33 ].…”

Section: Tumor Growth and Differentiation In Armsmentioning

confidence: 99%

“…TGF-β is known to strongly inhibit the proliferation of many cell types, including endothelial, epithelial, and immune cells, while playing a prominent role in controlling the differentiation of cell lineages during development [ 29 , 31 , 32 ]. Additionally, TGF-β family proteins are involved in other cellular functions such as promoting/protecting against cell death, cell motility, and invasion [ 29 , 31 , 33 ].…”

Section: Tumor Growth and Differentiation In Armsmentioning

confidence: 99%

Transforming Growth Factor Beta and Alveolar Rhabdomyosarcoma: A Challenge of Tumor Differentiation and Chemotherapy Response

Bhushan,

Iranpour,

Eshtiaghi

et al. 2024

IJMS

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Alveolar rhabdomyosarcoma (ARMS), an invasive subtype of rhabdomyosarcoma (RMS), is associated with chromosomal translocation events resulting in one of two oncogenic fusion genes, PAX3-FOXO1 or PAX7-FOXO1. ARMS patients exhibit an overexpression of the pleiotropic cytokine transforming growth factor beta (TGF-β). This overexpression of TGF-β1 causes an increased expression of a downstream transcription factor called SNAIL, which promotes epithelial to mesenchymal transition (EMT). Overexpression of TGF-β also inhibits myogenic differentiation, making ARMS patients highly resistant to chemotherapy. In this review, we first describe different types of RMS and then focus on ARMS and the impact of TGF-β in this tumor type. We next highlight current chemotherapy strategies, including a combination of the FDA-approved drugs vincristine, actinomycin D, and cyclophosphamide (VAC); cabozantinib; bortezomib; vinorelbine; AZD 1775; and cisplatin. Lastly, we discuss chemotherapy agents that target the differentiation of tumor cells in ARMS, which include all-trans retinoic acid (ATRA) and 5-Azacytidine. Improving our understanding of the role of signaling pathways, such as TGF-β1, in the development of ARMS tumor cells differentiation will help inform more tailored drug administration in the future.

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“…Later, in 1965, the clinical definition of MS, namely "central nervous system demyelinating diseases of unknown cause showing spatial and temporal multifocality", was established, and the current clinical picture of MS was largely established. Although the cause of MS is not yet clear, lesions are infiltrated by lymphocytes and macrophages, and inflammation mediated by an autoimmune mechanism is thought to cause demyelination [9]. In the human body, the immune system, centered on white blood cells and lymphocytes, works to protect itself from external enemies such as bacteria and viruses.…”

Section: Pathogenesis Of Msmentioning

confidence: 99%

Unraveling the Immunopathogenesis of Multiple Sclerosis: The Dynamic Dance of Plasmablasts and Pathogenic T Cells

Matsuzaka,

Yashiro

2023

Biologics

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Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system, characterized by multiple lesions occurring temporally and spatially. Additionally, MS is a disease that predominates in the white population. In recent years, there has been a rapid increase in the number of patients, and it often occurs in young people, with an average age of onset of around 30 years old, but it can also occur in children and the elderly. It is more common in women than men, with a male-to-female ratio of approximately 1:3. As the immunopathogenesis of MS, a group of B cells called plasmablasts controls encephalomyelitis via IL-10 production. These IL-10-producing B cells, called regulatory B cells, suppress inflammatory responses in experimental mouse models of autoimmune diseases including MS. Since it has been clarified that these regulatory B cells are plasmablasts, it is expected that the artificial control of plasmablast differentiation will lead to the development of new treatments for MS. Among CD8-positive T cells in the peripheral blood, the proportion of PD-1-positive cells is decreased in MS patients compared with healthy controls. The dysfunction of inhibitory receptors expressed on T cells is known to be the core of MS immunopathology and may be the cause of chronic persistent inflammation. The PD-1+ CD8+ T cells may also serve as indicators that reflect the condition of each patient in other immunological neurological diseases such as MS. Th17 cells also regulate the development of various autoimmune diseases, including MS. Thus, the restoration of weakened immune regulatory functions may be a true disease-modifying treatment. So far, steroids and immunosuppressants have been the mainstream for autoimmune diseases, but the problem is that this kills not only pathogenic T cells, but also lymphocytes, which are necessary for the body. From this understanding of the immune regulation of MS, we can expect the development of therapeutic strategies that target only pathogenic immune cells.

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Transforming growth factor β (TGF-β) pathway in the immunopathogenesis of multiple sclerosis (MS); molecular approaches

Cited by 5 publications

References 125 publications

25 Hydroxyvitamin D and Cytokine Profile in Patients With Relapsing-Remitting Multiple Sclerosis

25 Hydroxyvitamin D and Cytokine Profile in Patients With Relapsing-Remitting Multiple Sclerosis

Transforming Growth Factor Beta and Alveolar Rhabdomyosarcoma: A Challenge of Tumor Differentiation and Chemotherapy Response

Unraveling the Immunopathogenesis of Multiple Sclerosis: The Dynamic Dance of Plasmablasts and Pathogenic T Cells

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