ETA2022 Oral Presentations Oral Session 5: Autoimmunity (5 abstracts)
Update on the role of caveolin-1 in cell homeostasis and oxidative stress in hashimoto’s thyroiditis and graves’ disease
Marie-Christine Many 1 , Chantal Daumerie 2 , Antonella Boschi 3 , baldeschi lelio 3 , Mourad Michel 4 , Benoît Lengelé 5 , Behets Catherine 6 , Lancelot Marique 7 , Victoria Van Regemorter 7 , Werion Alexis 8 , Van Regemorter Elliott 9 , Hepp Michael 8 , de Bournonville Marc 8 , de Ville de Goyet Christine 8 & Julie Craps 10
1Faculté de Médecine, Irec Morf, Brussels, Belgium; 2Université Catholique de Louvain, Belgium; 3Cliniques Universitaires Saint-Luc, Ophtalmologie, Belgium; 4Cliniques Universitaires Saint-Luc, Endocrinologie, Brussels, Belgium; 5Université Catholique de Louvain, Morphologie Expérimentale, Bruxelles, Belgium; 6Université Catholique de Louvain, Brussels, Belgium; 7Université Catholique de Louvain; 8Ss/Mede/Irec/Ucl, Bruxelles, Belgium; 9Ucl, Brussels, Belgium; 10Ss/Mede/Irec/Ucl, Ss/Mede/Irec/Ucl, Bruxelles, Belgium
Caveolin-1 (cav1) is a member of the thyroxisome multiprotein complex required for thyroid hormones synthesis which is decreased in Hashimoto’s thyroiditis (HT) and excessive in Graves’ disease (GD). Both pathologies are characterized by oxidative stress (OS), the production of reactive oxygen species (ROS) exceeding the antioxidant defenses. The aim of this study is to correlate cav1 expression and OS in HT and GD. Primary cultures of human thyrocytes were treated or not with Th1 (Interleukin-1α and Interferonγ) or Th2 (Interleukin-4) cytokines. Thyroid samples from HT and GD patients were compared to paranodular tissues of patients with multinodular goiter (controls). Orbital fats were obtained from controls or patients with Graves’ orbitopathy (GO). Samples were processed for RT-PCR, Western blots or immunohistochemistry to analyze the expression of T4, cav1, 4-hydroxynonenal (HNE), caspase-6, catalase, peroxiredoxin 1 (PRDX1), sirtuin-1 (sirt1), NADPH oxidase (NOX)4 and NOX2. In HT, the glands comprised a mix of normal and altered follicles. The altered follicles, located within inflammatory zones, did not express cav1 and were unable to form and store T4 in the follicular lumen, T4 being detected inside the cytoplasm. They also highly expressed HNE, an OS marker, and presented numerous dead cells labelled with caspase-6. In primary cultures, Th1 cytokines decreased cav1 but also catalase and PRDX1 which detoxify H2O2 and sirt1 known to positively regulate antioxidants expression. At the opposite, in GD thyroids, all the follicles were able to form and store T4. Cav1 protein was increased as compared to controls and properly located at the apical pole. The high HNE expression indicative of OS correlated with an increase of NOX4 continually generating H2O2. However, antioxidants like catalase were upregulated to cope with ROS production so that there were few dead thyrocytes. Interleukin-4 which could mimic GD did not influence cav1 expression. Of interest, in GO orbital adipocytes, NOX4 was also increased, as well as NOX2, inducing OS further aggravated in these cells by a reduction of catalase. In conclusion, cav1 expression is diametrically opposed in HT and GD. In HT, the downregulation of cav1 by Th1 cytokines induces thyroxisome disruption, hypothyroidism and intracellular H202 production responsible for OS still aggravated by a Th1-induced decrease of sirt1 and antioxidant defenses. In GD, cav1 overexpression could be correlated with hyperthyroidism and NOX4 could be the prime target to prevent OS.
Volume 84
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Endocrine Abstracts
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