Transforming growth factor β1 (TGFβ1) mRNA level correlates with magnetic resonance imaging disease activity in Multiple Sclerosis patients

Bertolotto, Antonio; Capobianco, Marco; Malucchi, Simona; Manzardo, E.; Audano, Luisa; Bergui, Mauro; Bradac, Gianni Boris; Mutani, Roberto

doi:10.1016/s0304-3940(99)00102-0

Cited by 28 publications

(15 citation statements)

References 16 publications

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“…However, in a neurodegenerative disease model, transgenic overexpression of TGF-b1 in astrocytes exacerbates the disease pathology (WyssCoray et al 1997). In patients with multiple sclerosis, high levels of TGF-b1 mRNA expression in mononuclear peripheral cells have been associated with reduced disability, disease duration, and disease brain activity (Link et al 1994;Söderström et al 1995;Bertolotto et al 1999), although clinical trials of TGF-b treatment of patients with multiple sclerosis were terminated because of non-neurological toxicity (Wiendl et al 2000).…”

Section: Injury and Repairmentioning

confidence: 99%

TGF-β Family Signaling in Neural and Neuronal Differentiation, Development, and Function

Meyers

Kessler

2017

Cold Spring Harb Perspect Biol

138

107

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Section: Injury and Repairmentioning

confidence: 99%

TGF-β Family Signaling in Neural and Neuronal Differentiation, Development, and Function

Meyers

Kessler

2017

Cold Spring Harb Perspect Biol

138

107

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“…The role of cytokines in the pathogenesis of CNS disorders has been investigated in the peripheral blood, cerebrospinal fluid, and CNS tissue of various human diseases, including MS, subacute sclerosing panencephalitis, and acquired immune deficiency syndrome (6,32,47). In general, pro-inflammatory cytokines such as interleukin (IL)-1␤, IL-2, IL-6, IL-8, IL-12, tumor necrosis factor (TNF)-␣, and interferon (IFN)-␥ are associated with disease progression through attraction and activation of inflammatory cells and induction of nitric oxide in microglial cells and macrophages, whereas IL-10 and transforming growth factor (TGF)-␤ play an essential role in disease remission (10,11,13). In a previous study on the pathogenesis of demyelinating cerebellar lesions in DL, relative pro-inflammatory cytokine expression values were elevated simultaneously with the occurrence of CDV antigen, indicating that the virus itself directly triggered the upregulation of the pro-inflammatory cytokines (31).…”

Section: Introductionmentioning

confidence: 99%

Increase of Pro-Inflammatory Cytokine Expression in Non-Demyelinating Early Cerebral Lesions in Nervous Canine Distemper

et al. 2008

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Canine distemper virus (CDV) infection of the central nervous system results in lesions of the gray and white matter. While a biphasic disease process has been discussed for leukoencephalitis with a prominent loss of viral protein expression, polioencephalitis has been associated with virus persistence. Using semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR), expression of pro- and anti-inflammatory cytokines such as interleukin (IL)-1beta, IL-2, IL-6, IL-8, IL-10, IL-12, tumor necrosis factor-alpha (TNF)-alpha, interferon (IFN)-gamma, and transforming growth factor (TGF)-beta were studied in the cerebra of distemper dogs with white matter lesions in the cerebellum. Additionally, cytokine values were correlated with the degree of CDV infection, major histocompatibility complex class II (MHC II) expression, and infiltration of CD4-, CD8-, and CD3epsilon-positive lymphocytes. Cerebral CDV infection was not associated with detectable light microscopic lesions or infiltration of B and T lymphocytes. However, an increasing number of CDV-antigen-positive cells was associated with an upregulation of MHC II antigen. RT-PCR results revealed a significant upregulation of IL-6, IL-8, IL-12, and TNF-alpha in the cerebra of distemper dogs, whereas IL-10 and TGF-beta showed no significant increase. Elevated cytokine values were directly related to the presence of CDV antigen and MHC II upregulation. However, succeeding increases of the latter did not result in an additional proportional elevation of cytokine expression values. In summary, the present study demonstrates the expression of pro-inflammatory cytokines by resident neural cells following CDV infection. Furthermore, the lack of light microscopic changes indicates that additional factors besides cytokines are necessary for the development of a distemper-characteristic neuropathology.

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“…Several studies have demonstrated convincingly that TGF-␤ levels in serum and CSF from MS patients differ from those of controls. (7)(8)(9)(10)(11) Whether these observations reflect primary or secondary disease phenomena, however, remains to be answered. Second, as with most cytokines involved in MS pathogenesis, the specific role of TGF-␤ in MS can be highly variable.…”

Section: Discussionmentioning

confidence: 99%

“…(4)(5)(6) Furthermore, TGF-␤ levels in serum or cerebrospinal fluid (CSF) of MS patients differ significantly from those of controls and between disease stages, suggesting a possible influence of TGF-␤ on disease course. (7)(8)(9)(10)(11)(12) It is disappointing that attempts to link TGFB1 gene polymorphisms to MS have yielded mainly negative results. (13)(14)(15)(16) Recently, though, associations with TGFB1 gene polymorphisms have been reported in breast cancer, (17) diabetic nephropathy, (18) and Peyronie's disease.…”

Section: Introductionmentioning

confidence: 99%

Gender-Related Association Between the TGFBI+869 Polymorphism and Multiple Sclerosis

Schrijver¹,

Crusius²,

García-González³

et al. 2004

Journal of Interferon & Cytokine Research

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Our objective was to investigate whether polymorphisms and haplotypes in the TGFB1 gene are associated with susceptibility or disease characteristics of multiple sclerosis (MS). In 247 MS patients and 194 controls, single nucleotide polymorphisms (SNPs) at position +869 (Leu10Pro) and position +915 (Arg25Pro) in the signaling sequence of the TGFB1 gene were determined, and the distribution of alleles, genotypes, and haplotypes was related to clinical data. In addition, magnetic resonance imaging (MRI) data were studied in a subgroup of patients (n = 96). The allele distribution of the two polymorphisms studied was in Hardy-Weinberg equilibrium in patients and in controls. No association was found with any of the three haplotypes found in the Dutch population, denoted as haplotype 1 (TGFB1+869T-TGFB1+915G), haplotype 2 (TGFB1+869C-TGFB1+915G), and haplotype 3 (TGFB1+869C-TGFB1+915C). However, the TGFB1+869 genotype CC was significantly more frequent in patients (p = 0.031, chi2 test). The highest frequency of the TGFB1+869 genotype CC was observed in male patients (25.2% vs. 10.0% in controls, p = 0.004, chi2 test), and carriership of TGFB1+869 allele C was correspondingly increased in male patients (74.8% vs. 56.7%, p = 0.008, chi2 test, OR 2.27, 95% CI 1.23-4.17). Although there was no association with clinical markers of disease progression, patients homozygous for TGFB1+869 allele C showed a significantly higher annual increase in two MRI parameters: ventricular fraction (central atrophy) and T1-hypointense lesion load (matrix destruction). The TGFB1 T+869C (Leu10Pro) gene polymorphism is associated with MS susceptibility, especially in males, and with a more destructive course of the disease as illustrated by MRI.

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Transforming growth factor β1 (TGFβ1) mRNA level correlates with magnetic resonance imaging disease activity in Multiple Sclerosis patients

Cited by 28 publications

References 16 publications

TGF-β Family Signaling in Neural and Neuronal Differentiation, Development, and Function

TGF-β Family Signaling in Neural and Neuronal Differentiation, Development, and Function

Increase of Pro-Inflammatory Cytokine Expression in Non-Demyelinating Early Cerebral Lesions in Nervous Canine Distemper

Gender-Related Association Between the TGFBI+869 Polymorphism and Multiple Sclerosis

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