Quantitation of glucocorticoid receptor alpha and NF-κB pathway mRNA and its correlation with disease activity in rheumatoid arthritis patients

Cavalcante, L. O.; Melo, Murilo Rezende; Dinis, Valquíria Garcia; Castro, R. B.; Souza, Branca Dias Batista de; Longui, Carlos Alberto

doi:10.4238/vol9-4gmr970

Cited by 12 publications

(13 citation statements)

References 26 publications

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“…In addition, no correlation occurred between GRα or NF-κB expression and cortisol suppression after the VLD-IV-DST in patients or controls, which correlates to observations published by Cavalcante et al (2010). However, RA may present greater differences in inflammation between synovia and PBMCs, and due to the systemic involvement in SLE, PBMC gene expression may better reflect inflammation status.…”

Section: Discussionsupporting

confidence: 85%

“…Significant reduction of ACTH and cortisol concentrations occurred after VLD-IV-DST, indicating that this test was effective in establishing a spectrum of sensitivity to GC in vivo as previously demonstrated (Faria et al, 2008;Cobra et al, 2009;Cavalcante et al, 2010). However, the extent of suppression was lower in patients than in controls (23.48 vs 53.2%, respectively), indicating lower GC sensitivity in SLE patients during the remission phase of the disease.…”

Section: Discussionsupporting

confidence: 61%

“…SYBR Green, an intercalating, nonspecific dye detection system was used for the quantitation of NF-κB. For NF-κB, primer concentrations were adjusted to 0.3 μL of each primer (final concentration, 120 nM), with a corresponding increase in water (9.9 mL) in each reaction (Cavalcante et al, 2010).…”

Section: Grα and Nf-κb Mrna Determination Through Real-time Quantitatmentioning

confidence: 99%

“…Another study (Cavalcante et al, 2010) has shown that GC sensitivity evaluated by the percentage of cortisol reduction after a very-low-dose intravenous dexamethasone suppression test (VLD-IV-DST), as well as NF-κB, IKK, c-Fos (proto-oncogene), and GRα mRNA expression, were similar in RA patients and controls.…”

Section: Introductionmentioning

confidence: 99%

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Persistent glucocorticoid resistance in systemic lupus erythematosus patients during clinical remission

Melo¹,

Melo²,

Saramago³

et al. 2013

Genet. Mol. Res.

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ABSTRACT. Glucocorticoids (GCs) are key drugs in the treatment of systemic lupus erythematosus (SLE). GC dose reduction during remission is related to disease activity, GC dose used, length of treatment, and individual GC sensitivity. We compared GC receptor α (GRα) isoform and nuclear factor kappaB (NF-κB) messenger RNA quantitation and in vivo GC sensitivity between SLE patients during remission and healthy controls. We performed a cross-sectional study of 19 women aged 22-49 years, including 9 SLE patients in clinical remission taking ≤5 mg prednisone and 10 matched controls. We evaluated GC sensitivity using 2 cortisol suppression tests: a very-low-dose intravenous dexamethasone suppression test (VLD-IV-DST) and a low-dose oral dexamethasone suppression test. GRα and NF-κB mRNA were quantified using real-time polymerase chain reaction. Although basal cortisol and adrenocorticotropic hormone levels were similar between the groups, the percentage of cortisol reduction after the VLD-IV-DST was 56% lower in SLE patients than in controls (P = 0.014). GRα and NF-κB gene expression levels were similar between the groups. The low-dose oral dexamethasone test caused intense cortisol suppression in all individuals, limiting the ability of this test to discriminate individual GC sensitivity. A positive correlation was found between the extent of cortisol suppression in vivo (VLD-IV-DST) and the number of days elapsed since the last flare of lupus activity. Despite clinical remission, SLE patients displayed partial GC resistance recognized by the VLD-IV-DST. The mechanism of this resistance is unrelated to altered GRα and NF-κB mRNA expression.

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Section: Discussionsupporting

confidence: 85%

Section: Discussionsupporting

confidence: 61%

Section: Grα and Nf-κb Mrna Determination Through Real-time Quantitatmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Persistent glucocorticoid resistance in systemic lupus erythematosus patients during clinical remission

Melo¹,

Melo²,

Saramago³

et al. 2013

Genet. Mol. Res.

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“…Induction of pro-inflammatory mediators requires activation of the nuclear factor (NF)-κB inducing kinase-or inhibitor of NF-κB (IκB) kinase-mediated NF-κB signal transduction pathways (6,7). The transcription factor NF-κB has been well recognized as a key regulator of inflammation in RA (8)(9)(10).…”

Section: Introductionmentioning

confidence: 99%

Altered TNFAIP3 mRNA expression in peripheral blood mononuclear cells from patients with rheumatoid arthritis

et al. 2015

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Abstract. The tumor necrosis factor α-induced protein-3 (TNFAIP3) gene functions in negative immunoregulation and its single-nucleotide polymorphisms (SNPs) are associated with rheumatoid arthritis (RA) disease. However, its expression level in immune cells from RA patients remains unclear. The aim of the present study was to investigate whether the expression of TNFAIP3 is changed in patients with RA. Reverse transcription-quantitative polymerase chain reaction analysis was used to determine TNFAIP3 mRNA expression in peripheral blood mononuclear cells (PBMCs) from patients with RA and healthy controls. TNFAIP3 expression was decreased in RA patients compared with the healthy controls. The expression level of the TNFAIP3 gene negatively correlated with the RA score, anti-cyclic citrullinated peptide (CCP) antibody levels and C-reactive protein levels. Furthermore, RA patients with positive results of anti-CCP antibodies had a lower expression of TNFAIP3 than those without anti-CCP antibodies. In conclusion, the present results suggest that the insufficient expression of the TNFAIP3 gene in PBMCs may correlate with the diagnosis of RA. IntroductionRheumatoid arthritis (RA) is a common chronic inflammatory disease that predominantly affects the small joints of the hands and feet (1). The propagation of inflammation is characterized by migration of mononuclear cells into the local inflammatory sites, leading to the hyperplasia of fibroblast-like synoviocytes (FLSs) primarily due to resistance to apoptosis and damage to cartilage and bone (2). The chronic inflammation is attributed to breakdown of immune homostasis, which results in activation of immune cells and elevation of pro-inflammatory cytokines (3). The immune activation leads to deposition of immune complexes and mononuclear cell infiltration into susceptible organs, while the pro-inflammatory cytokines are responsible for maintenance of the immune activation (4). The major mediators of chronic inflammation in RA include tumor necrosis factor α (TNF-α), interleukin (IL)-1β, IL-6, IL-8 and prostaglandin E2 (5). Induction of pro-inflammatory mediators requires activation of the nuclear factor (NF)-κB inducing kinase-or inhibitor of NF-κB (IκB) kinase-mediated NF-κB signal transduction pathways (6,7). The transcription factor NF-κB has been well recognized as a key regulator of inflammation in RA (8-10).TNF-α-induced protein-3 (TNFAIP3) is an important negative immunoregulatory gene. TNFAIP3 is a dual ubiquitin-editing enzyme, whose expression is induced by a large number of stimuli in a wide variety of cells (11). Evidence from animal models indicates that TNFAIP3 is a plausible candidate gene in RA susceptibility (11). In TNFAIP3 knockout mice, its deficiency leads to death shortly following birth by severe inflammation and tissue damage in multiple organs (12,13). In immune cells, overexpression of TNFAIP3 can terminate NF-κB signaling transduced from TNF receptors, toll-like receptors, nucleotide-binding oligomerization domain containing 2 receptors or T ...

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Effect of prednisone treatment for 30 and 90 days on bone metabolism in collagen-induced arthritis (CIA) rats

Zhang

Min

et al. 2017

J Bone Miner Metab

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Glucocorticoids (GCs) are often prescribed to treat rheumatoid arthritis (RA) in the long term, but there is still controversy in the administration of GCs, mainly because of the adverse reactions such as osteoporosis. Numerous studies have demonstrated that osteoporosis could be induced by GCs in normal rats. However, few experiments have focused on whether osteoporosis could be induced or aggravated by GCs in collagen induced arthritis (CIA) rats. We have investigated bone changes in CIA rats treated with prednisone at 4.5 mg/kg/day for 30 and 90 days by bone histomorphometry, bone mineral density (BMD), micro-CT, biomechanical test, and enzyme-linked immunosorbant assay. We found that high bone turnover osteoporosis was shown in CIA rats. Prednisone treatment for 30 and 90 days improved articular structure and decelerated the degeneration of the femur in CIA rats, but did not improve BMD and bone biomechanics. We conclude that osteoporosis was not aggravated in CIA rats treated with prednisone for 30 and 90 days. On the contrary, prednisone treatment for 30 and 90 days could prevent bone loss of the femur in CIA rats. There was a negative effect on bone metabolism in CIA rats treated with prednisone for 90 days.

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Quantitation of glucocorticoid receptor alpha and NF-κB pathway mRNA and its correlation with disease activity in rheumatoid arthritis patients

Cited by 12 publications

References 26 publications

Persistent glucocorticoid resistance in systemic lupus erythematosus patients during clinical remission

Persistent glucocorticoid resistance in systemic lupus erythematosus patients during clinical remission

Altered TNFAIP3 mRNA expression in peripheral blood mononuclear cells from patients with rheumatoid arthritis

Effect of prednisone treatment for 30 and 90 days on bone metabolism in collagen-induced arthritis (CIA) rats

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