TNFα-mediated activation of NF-κB downregulates sodium-iodide symporter expression in thyroid cells

Faria, Márcia; Domingues, Rita; Paixão, Francisca Ventura; Bugalho, Maria João; Matos, Paulo; Silva, Ana Luísa

doi:10.1371/journal.pone.0228794

Cited by 13 publications

(12 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Then, the mRNA expression of iNOS was increased and that of Arg-1 was decreased in the PMA group compared with the Sal B group. PMA has been shown to induce canonical NF-κB-dependent transcription by acting through the direct activation of protein-kinase-C 56 , 57 . Moreover, the ELISA results indicated that the TNF-α and IL-6 levels were increased, and the IL-10 level was decreased.…”

Section: Discussionmentioning

confidence: 99%

Salvianolic acid B inhibits RAW264.7 cell polarization towards the M1 phenotype by inhibiting NF-κB and Akt/mTOR pathway activation

Zou

Gao

et al. 2022

Sci Rep

View full text Add to dashboard Cite

M1 macrophages secrete a large number of proinflammatory factors and promote the expansion of atherosclerotic plaques and processes. Salvianolic acid B (Sal B) exerts anti-inflammatory, antitumor and other effects, but no study has addressed whether Sal B can regulate the polarization of macrophages to exert these anti-atherosclerotic effects. Therefore, we investigated the inhibition of Sal B in M1 macrophage polarization and the underlying mechanism. The effects of different treatments on cell viability, gene expression and secretion of related proteins, phenotypic markers and cytokines were detected by MTT and western blot assays, RT‒qPCR and ELISAs. Cell viability was not significantly changed when the concentration of Sal B was less than 200 μM, and Lipopolysaccharide (LPS) (100 ng/mL) + interferon-γ (IFN-γ) (2.5 ng/mL) successfully induced M1 polarization. RT‒qPCR and ELISAs indicated that Sal B can downregulate M1 marker (Inducible Nitric Oxide Synthase (iNOS), Tumor Necrosis Factor-α (TNF-α), and Interleukin-6 (IL-6)) and upregulate M2 marker (Arginase-1 (Arg-1) and Interleukin-10 (IL-10)) expression. Western blotting was performed to measure the expression of Nuclear Factor-κB (NF-κB), p-Akt, p-mTOR, LC3-II, Beclin-1, and p62, and the results suggested that Sal B inhibits the M1 polarization of RAW264.7 macrophages by promoting autophagy via the NF-κB signalling pathway. The study indicated that Sal B inhibits M1 macrophage polarization by inhibiting NF-κB signalling pathway activation and downregulating Akt/mTOR activation to promote autophagy.

show abstract

Section: Discussionmentioning

confidence: 99%

Salvianolic acid B inhibits RAW264.7 cell polarization towards the M1 phenotype by inhibiting NF-κB and Akt/mTOR pathway activation

Zou

Gao

et al. 2022

Sci Rep

View full text Add to dashboard Cite

show abstract

“…Higher NIS expression is associated with higher uptake of 131 I by thyroid cell [18], [34]. Thyroid cells that do not respond to radioiodine can be lost NIS expression [15], [17], [23], [24]. The availability of specific polyclonal and monoclonal anti-hNIS antibodies has allowed the investigation of NIS protein expression levels in various thyroid tissues.…”

Section: Discussionmentioning

confidence: 99%

“…On the other hand, some thyroid cancers and metastases showed low uptake of 131 I compare to healthy thyroid tissues [16]. One-third of advanced DTC metastases show low avidity to iodine [8], [17], [18], [19]. Losing the ability to concentrate iodine can occur during the progression of the disease.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Evaluating the Natrium Iodide Symporter Expressions in Thyroid Tumors

Elliyanti

Rustam

Tofrizal

et al. 2021

Open Access Maced J Med Sci

View full text Add to dashboard Cite

BACKGROUND: Decreased Natrium iodide symporter (NIS) expression levels or diminished NIS targeting thyroid cancer cells’ plasma membrane leads to radioiodine-refractory disease. AIM: The aim of this study was to analyze the NIS expression in thyroid tumors. MATERIALS AND METHODS: The samples were thyroid tissues of patients who underwent surgery for a thyroid tumor. The tissues were processed for NIS protein expressions by immunohistochemistry (IHC) and Western blot (WB). Graves’ disease samples were used as positive controls. The samples were incubated without the primary antibody, and they were used as negative controls for IHC examination. Na+/K+ ATPase was a plasma membrane protein marker in the WB procedure. RESULTS: Twenty-nine samples were assessed for NIS protein. All of them showed the expression in the cytoplasm with intensity 1+ to 3+ with Allred score 3-8. Fourteen out of 29 cases (48.2%) showed NIS cytoplasm staining intensity ≥2+ consist of 10 papillary thyroid cancer (PTC), three follicular thyroid cancer, and one adenoma. Membrane staining was found in 2 samples of PTC (6.9%). Six samples (adenoma 1 sample, PTC 5 samples) showed NIS expression at membrane very weak (1+); they were considered as negative. NIS protein has several bands of ~ 80 kDa, ~ 62 kDa, and ~ 49 kDa. CONCLUSION: NIS expression in thyroid cancer mostly expresses in the cytoplasm instead of the membrane. NIS will play a functional role in the membrane to bring iodine across the membrane against the concentration. It can be the main reason for the lack of response of radioiodine in some differentiated thyroid cancers.

show abstract

“…Second, we added dexamethasone (from day 30) and the TGFb inhibitor SB431542 (from day 37), based on transcriptomic data showing substantial levels of TGFb pathway markers (Extended data Fig. 2f) among NKX2-1 cells, and the known inhibition of thyroid differentiation by inflammation and TGFb pathway stimulation [27][28][29][30][31] .…”

Section: Induction Of Thyroid Statusmentioning

confidence: 99%

Transplantable human thyroid organoids generated from embryonic stem cells to rescue hypothyroidism

Romitti¹,

Fonseca²,

Doumont³

et al. 2021

Preprint

View full text Add to dashboard Cite

The function of the thyroid gland is to capture iodide in order to synthesize hormones that act on almost all tissues and are essential for normal growth and metabolism. Low plasma levels of thyroid hormones lead to hypothyroidism, which is one of the most common disorder in humans which is not always satisfactorily treated by lifelong hormone replacement. Therefore, in addition to the lack of in vitro tractable models to study human thyroid development, differentiation and maturation, there is a need for new therapeutic approaches that involve replacement of thyroid tissue responsive to changing demands for thyroid hormone. Here we report the first transplantable thyroid organoids derived from human embryonic stem cells capable of restoring plasma thyroid hormone to athyreotic mice as a proof of concept for future therapeutic development.

show abstract

TNFα-mediated activation of NF-κB downregulates sodium-iodide symporter expression in thyroid cells

Cited by 13 publications

References 47 publications

Salvianolic acid B inhibits RAW264.7 cell polarization towards the M1 phenotype by inhibiting NF-κB and Akt/mTOR pathway activation

Salvianolic acid B inhibits RAW264.7 cell polarization towards the M1 phenotype by inhibiting NF-κB and Akt/mTOR pathway activation

Evaluating the Natrium Iodide Symporter Expressions in Thyroid Tumors

Transplantable human thyroid organoids generated from embryonic stem cells to rescue hypothyroidism

Contact Info

Product

Resources

About