Caveolin-1 Regulates CCL5 and PPARγ Expression in Nthy-ori 3-1 Cells: Possible Involvement of Caveolin-1 and CCL5 in the Pathogenesis of Hashimoto’s Thyroiditis

Abstract

Background: Hashimoto’s thyroiditis (HT) is characterized by lymphocytic infiltration of the thyroid parenchyma, which ultimately leads to tissue destruction and loss of function. Caveolin-1 (Cav-1) is an essential structural constituent of lipid rafts in the plasma membrane of cells and is reported to be significantly reduced in thyrocytes from HT patients. However, the mechanism of Cav-1 involvement in HT pathogenesis is still largely unclear. Methods: Cav-1 expression in thyroid tissues from HT patients and euthyroid nodular goiter tissues was detected by immunohistochemistry staining. Cav-1 knockdown and overexpression were constructed by lentiviral transfection in the human thyroid follicular epithelial cell (TFC) line of Nthy-ori 3-1. The mRNA expression levels of chemokines in TFCs were determined by quantitative real-time PCR (qPCR). Cav-1 and peroxisome proliferator-activated receptor gamma (PPARγ) levels were analysed by qPCR and Western blot analysis. The migration ability of peripheral blood mononuclear cells (PBMCs) was detected by the Transwell assay. Results: In this study, Cav-1 and PPARγ expression was reduced in the thyroid tissues from HT patients. In vitro experiments showed that the expressions of chemokine (C-C motif) ligand 5 (CCL5) and migration of PBMCs were markedly increased, while the level of PPARγ was significantly decreased after the lentivirus-mediated knockdown of Cav-1 in Nthy-ori 3-1 cells. Interestingly, pioglitazone, a PPARγ agonist, not only upregulated PPARγ and Cav-1 proteins significantly, but also effectively reversed the Cav-1-knockdown-induced upregulation of CCL5 in Nthy-ori 3-1 cells and reduced the infiltration of lymphocytes. Conclusion: The inhibition of Cav-1 upregulated the CCL5 expression and downregulated the PPARγ expression in TFC while pioglitazone, a PPARγ agonist, reversed the detrimental consequence. This outcome might be a potential target for the treatment of lymphocyte infiltration into the thyroid gland and HT development.

Gene expression in meningeal lymphatic endothelial cells following traumatic brain injury in mice

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Comprehensive analysis of lncRNA-mediated ceRNA regulatory networks and key genes associated with papillary thyroid cancer coexistent with Hashimoto’s thyroiditis

“…The TSH-lowering effect of selenium supplementation is unlikely to be related to changes in humoral markers of autoimmunity and/or circulating CXCL9 [ 43 ]. In vitro experiments showed that the expressions of CCL5 and migration of peripheral blood mononuclear cells were markedly increased, while the level of PPARγ was significantly decreased after the lentivirus-mediated knockdown of Cav-1 in Nthy-ori 3–1 cells [ 44 ].…”

Bioinformatics Analysis of the Cross-talk Between Idiopathic Pulmonary Fibrosis and Hashimoto's Thyroiditis on the Hub Genes and Key Pathways

“…which reduces the intrinsic antiviral response, stimulates the recruitment of inflammatory lymphocytes, and promotes inflammatory changes [17]. Numerous studies have demonstrated a positive correlation between increased CCL5 expression with inflammatory infiltration in HT patients [18][19][20] and pulmonary fibrosis patients [21].CD68 expression was increased in patients with HT [22] and IPF [23], which may be related to immune processes. An association between the increased CD68positive cells and the increased percentage of lung tissue in IPF patients was found [24].…”