The relationship between transforming growth factor-β1, vascular endothelial growth factor, nitric oxide and Hashimoto's thyroiditis

Vural, Pervin; Değirmencioğlu, Sevgin; Erden, Sacide; Gelincik, Aslı

doi:10.1016/j.intimp.2008.11.003

Cited by 27 publications

(23 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…A single study of the Greece population by Vazgiourakis et al 2007 showed a significant association of the 27 bp VNTR with RA [18]. Previously, a possible relationship between the synthesis of nitric oxide by the eNOS gene and immune dysregulation in the thyroid gland was reported by Varul et al [10]. Our study further strengthens this finding by demonstrating a statistically significant association between HT patients and the eNOS-27 bp repeat polymorphism.…”

Section: Discussionsupporting

confidence: 87%

“…Oxidative stress was reported to be increased and more profound in RA than SLE and could well reflect disease activity [11]. Increased nitric oxide levels have also been observed in HT patients [10]. Increased production of nitric oxide may disrupt T cell activation, differentiation and effector responses; each of which may contribute to autoimmunity in HT [41].…”

Section: Discussionmentioning

confidence: 99%

“…Similarly, an increased concentration of NO have been correlated with disease severity in RA patients and is, in turn, regarded as a key mediator of apoptosis within the joints of RA patients [7][8][9]. Addi-tionally, increased NO levels have also been reported in hashimoto's thyroiditis (HT) patients [10].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Influence of Endothelial Nitric Oxide Synthase Gene Intron-4 27bp Repeat Polymorphism on Its Expression in Autoimmune Diseases

AlFadhli

2013

Disease Markers

View full text Add to dashboard Cite

Abstract. The purpose of this study was to analyse the effect of the T-786C polymorphism and intron 4 27 bp variable number tandem repeat(VNTR) eNOS markers for their potential association with Systemic Lupus Erythematosus(SLE), Hashimotos thyroiditis(HT) and Rheumatoid arthritis(RA) as well as to explore their effect on eNOS mRNA expression and nitrate production (NOx). Kuwaitis (n = 383) matched by age, gender and ethnicity were genotyped by fluorescent-labelled-restriction fragment length polymorphism (RFLP) and fragment analysis. Expression of eNOS mRNA was analysed using RT-PCR and sera from subjects were screened for NOx using ELISA. Analysis of the allelic frequency revealed a significant association of the 4b allele with susceptibility to SLE (p = 0.0092, OR = 1.76). The 4bb genotype was found to be associated with SLE (p = 0.0076, OR = 1.97) and HT (p = 0.05, OR = 1.81). Allelic and genotypic distribution did not differ between RA patients and healthy control subjects. The 4bb genotype resulted in reduced expression of eNOS mRNA in SLE, RA and HT, but only the reduction in HT was significant (p = 0.05). The 4ab genotype revealed a significant association with increased eNOS expression in HT (p = 0.03) and RA (p = 0.014) patients, and elevated NOx levels were detected in the autoimmune disease cohorts (p < 0.05) when compared to healthy control subjects. The T-786C SNP failed to show a significant association (p > 0.05) with SLE, HT, and RA patients. This study is the first to reveal a significant association between the 4bb genotype of the 27 bp VNTR and susceptibility to HT. The expression of eNOS is related to the number of 27 bp repeats, with heterozygous 4bb repeats showing a decrease in eNOS expression. eNOS -endothelial nitric oxide synthase.

show abstract

Section: Discussionsupporting

confidence: 87%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Influence of Endothelial Nitric Oxide Synthase Gene Intron-4 27bp Repeat Polymorphism on Its Expression in Autoimmune Diseases

AlFadhli

2013

Disease Markers

View full text Add to dashboard Cite

show abstract

“…After initiation of the autoreactive immune response by CD4 + T cells, the expansion of T cell populations results in a massive lymphocyte accumulation in patients' thyroids (23,24). Moreover, it has recently been demonstrated that the serum concentration of TGF-1b is decreased in HT (25), and that some Treg subsets apparently exert a defective suppressive function in these patients. Being that PKCε is implicated in the response of CD4 T cells to both CD3-mediated proliferative stimuli and TGF-1b antiproliferative signals, we were not surprised to find significantly higher expression levels of PKCε in HT patients than in HC.…”

Section: Discussionmentioning

confidence: 99%

“…After initiation of the autoreactive immune response by CD4 + T cells, the expansion of autoreactive T cell populations, prolonging the inflammatory response, results in a massive lymphocyte accumulation in patients' thyroids (23,24). It has recently been demonstrated that the serum concentration of TGF-1b is decreased in HT (25), and that in patients with HT and Graves' disease, some Treg subsets apparently exert a defective suppressive function (26).…”

mentioning

confidence: 99%

Protein Kinase Cε Regulates Proliferation and Cell Sensitivity to TGF-1β of CD4+ T Lymphocytes: Implications for Hashimoto Thyroiditis

Mirandola

Gobbi

Masselli

et al. 2011

The Journal of Immunology

View full text Add to dashboard Cite

We have studied the functional role of protein kinase Cε (PKCε) in the control of human CD4+ T cell proliferation and in their response to TGF-1β. We demonstrate that PKCε sustains CD4+ T cell proliferation triggered in vitro by CD3 stimulation. Transient knockdown of PKCε expression decreases IL-2R chain transcription, and consequently cell surface expression levels of CD25. PKCε silencing in CD4 T cells potentiates the inhibitory effects of TGF-1β, whereas in contrast, the forced expression of PKCε virtually abrogates the inhibitory effects of TGF-1β. Being that PKCε is therefore implicated in the response of CD4 T cells to both CD3-mediated proliferative stimuli and TGF-1β antiproliferative signals, we studied it in Hashimoto thyroiditis (HT), a pathology characterized by abnormal lymphocyte proliferation and activation. When we analyzed CD4 T cells from HT patients, we found a significant increase of PKCε expression, accounting for their enhanced survival, proliferation, and decreased sensitivity to TGF-1β. The increased expression of PKCε in CD4+ T cells of HT patients, which is described for the first time, to our knowledge, in this article, viewed in the perspective of the physiological role of PKCε in normal Th lymphocytes, adds knowledge to the molecular pathophysiology of HT and creates potentially new pharmacological targets for the therapy of this disease.

show abstract

Four kinds of hypothyroidism and the cancers of breast and lung found in cases of Japanese rheumatoid arthritis (RA), arthritis deformans, or bone fracture

Nakatsuji

2009

Comp Clin Pathol

View full text Add to dashboard Cite

The relationship between transforming growth factor-β1, vascular endothelial growth factor, nitric oxide and Hashimoto's thyroiditis

Cited by 27 publications

References 34 publications

Influence of Endothelial Nitric Oxide Synthase Gene Intron-4 27bp Repeat Polymorphism on Its Expression in Autoimmune Diseases

Influence of Endothelial Nitric Oxide Synthase Gene Intron-4 27bp Repeat Polymorphism on Its Expression in Autoimmune Diseases

Protein Kinase Cε Regulates Proliferation and Cell Sensitivity to TGF-1β of CD4+ T Lymphocytes: Implications for Hashimoto Thyroiditis

Four kinds of hypothyroidism and the cancers of breast and lung found in cases of Japanese rheumatoid arthritis (RA), arthritis deformans, or bone fracture

Contact Info

Product

Resources

About