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.