Smoking Induces Overexpression of Immediate Early Genes in Active Graves' Ophthalmopathy

Planck, Tereza; Shahida, Bushra; Parikh, Hemang; Ström, Kristoffer; Åsman, Peter; Brorson, Håkan; Hallengren, Bengt; Lantz, Mikael

doi:10.1089/thy.2014.0153

Cited by 30 publications

(24 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…We have recently demonstrated that several immediate early genes including CYR61, EGR1 and COX-2 are overexpressed in orbital tissue of smokers with severe GO as compared to nonsmokers [21]. Tobacco smoking is a risk factor for development of both GD and GO, and it was stated in a recent review that current smoking increases the risk of GD approximately twofold and GO approximately threefold [3].…”

Section: Discussionmentioning

confidence: 99%

Adjuvant Treatment of Graves' Disease with Diclofenac: Safety, Effects on Ophthalmopathy and Antibody Concentrations

et al. 2016

Self Cite

View full text Add to dashboard Cite

Background: Orbital morphological changes are often present in patients with Graves' disease (GD) already at diagnosis, and cyclooxygenase type 2 (COX-2) is overexpressed in active Graves' ophthalmopathy (GO). Objective: To investigate if adjuvant treatment of GD with the COX inhibitor and peroxisome proliferator-activated receptor-γ (PPAR-γ) antagonist diclofenac decreases the development of ophthalmopathy and if laboratory parameters are affected. Methods: This is a multicenter trial where 61 subjects were randomized to methimazole (block and replace with L-thyroxine) either with or without diclofenac 50 mg 1 × 2 for 12 months. The primary end point development of GO after 24 months was evaluated. Smoking habits were registered and the thyroid parameters TSH, free T₄, free T₃, TSH receptor antibodies (TRAb) and anti-TPO were followed. Safety parameters (kidney, liver and blood) and adverse events were regularly registered. Results: GO developed in 11% (n = 3) of the patients treated with diclofenac and in 21% (n = 6) of the controls (p = 0.273). The adverse event profile was acceptable without any severe events related to diclofenac. Both TRAb and anti-TPO concentrations decreased during treatment with methimazole, but the anti-TPO concentrations were lower in patients treated with diclofenac after 15 months (p = 0.031). The TRAb concentrations were not significantly changed between groups. Smokers had higher concentrations of TRAb than nonsmokers both at diagnosis of GD (p = 0.048) and after 15 months (p = 0.042). Conclusions: Treatment with diclofenac had no significant influence on development of GO. Diclofenac reduces anti-TPO concentrations and seems to be safe to use in GD patients.

show abstract

Section: Discussionmentioning

confidence: 99%

Adjuvant Treatment of Graves' Disease with Diclofenac: Safety, Effects on Ophthalmopathy and Antibody Concentrations

et al. 2016

Self Cite

View full text Add to dashboard Cite

show abstract

“…36 Upregulation of several adipocyte regulatory genes including PPARc, adiponectin, and leptin support increased de novo adipogenesis and/or fat cell expansion in TO. 6 In addition, adipogenesis may be regulated through Wnt-signaling with dysregulation of secreted frizzled-related protein-1, Wnt5a, sFRPs, and DKK.…”

Section: Discussionmentioning

confidence: 99%

Differential Gene Expression Profiling of Orbital Adipose Tissue in Thyroid Orbitopathy

Khong

Wang

Smyth

et al. 2015

Invest. Ophthalmol. Vis. Sci.

View full text Add to dashboard Cite

PURPOSE. We aimed to determine differentially expressed genes relevant to orbital inflammation and orbital fat expansion in thyroid orbitopathy (TO) using microarray gene profiling in a case-control study.METHODS. Human orbital adipose samples were obtained from individuals with active TO (n ¼ 12), inactive TO (n ¼ 21), and normal controls (n ¼ 21). Gene expression profiles were examined using microarray analysis and were compared between active and inactive TO, and between active TO and normal controls. Top ranked differentially expressed genes were validated by real-time RT-PCR in an additional eight active TO, 13 inactive TO, and 11 normal controls and correlated with gene set enrichment analysis (GSEA) and molecular pathways analysis.RESULTS. Seven hundred twenty-one probes (683 genes) and 806 probes (735 genes) were significantly differentially expressed in comparing active to inactive TO and in comparing active TO to healthy controls, respectively. All selected genes were confirmed to be differentially expressed by real-time RT-PCR. Multiple top ranked genes in active versus inactive TO comparison are overrepresented by immune and inflammatory response genes. They include defensins (DEFA1, DEFA1B, DEFA3), which were overexpressed by 3.05-to 4.14-fold and TIMD4 by 4.20-fold. Markers for adipogenesis were overexpressed including SCD, FADS1, and SCDP1. Gene set enrichment analysis revealed dysregulation of epigenetic signatures, T-cell activation, Th1 differentiation, defensin pathway, cell adhesion, cytoskeleton organization, apoptosis, cell cycling, and lipid metabolism in active TO.CONCLUSIONS. Active TO is characterized by upregulation of genes involved in cell-mediated immune, innate immune, and inflammatory response and enhanced orbital adipogenesis. TIMD4, DEFA1, DEFA1B, and DEFA3 genes may be involved in the innate immune-mediated orbital inflammation in TO. Epigenetic mechanisms may play a role in the pathogenesis of TO.

show abstract

“…Smoking is related to an increased risk of Graves’ hyperthyroidism (twofold), GO (three to four times), or relapse of GD or GO (48, 49), and it is linked to a more severe GO. Many different hypotheses about how smoking may enhance the risk of GD or GO have been reported (50–58). …”

Section: Environmental Factorsmentioning

confidence: 99%

Environmental Issues in Thyroid Diseases

et al. 2017

View full text Add to dashboard Cite

Environmental factors are determinant for the appearance of autoimmune thyroid diseases (AITD) in susceptible subjects. Increased iodine intake, selenium, and vitamin D deficiency, exposure to radiation, from nuclear fallout or due to medical radiation, are environmental factors increasing AITD. Cigarette smoking is associated with Graves’ disease and Graves’ ophthalmopathy, while it decreases the risk of hypothyroidism and thyroid autoimmunity. Viral infections are important environmental factors in the pathogenesis of AITD, too, particularly human parvovirus B19 (EVB19) and hepatitis C virus. Among the many chemical contaminants, halogenated organochlorines and pesticides variably disrupt thyroid function. Polychlorinated biphenyls and their metabolites and polybrominated diethyl ethers bind to thyroid transport proteins, such as transthyretin, displace thyroxine, and disrupt thyroid function. Among drugs, interferon- and iodine-containing drugs have been associated with AITD. Moreover intestinal dysbiosis causes autoimmune thyroiditis. To reduce the risk to populations and also in each patient, it is necessary to comprehend the association between environmental agents and thyroid dysfunction.

show abstract

Smoking Induces Overexpression of Immediate Early Genes in Active Graves' Ophthalmopathy

Cited by 30 publications

References 40 publications

Adjuvant Treatment of Graves' Disease with Diclofenac: Safety, Effects on Ophthalmopathy and Antibody Concentrations

Adjuvant Treatment of Graves' Disease with Diclofenac: Safety, Effects on Ophthalmopathy and Antibody Concentrations

Differential Gene Expression Profiling of Orbital Adipose Tissue in Thyroid Orbitopathy

Environmental Issues in Thyroid Diseases

Contact Info

Product

Resources

About