TNF-alpha is upregulated in subacute thyroiditis and stimulates expression of miR-155-5p in thyroid follicle cells.

Tumor necrosis factor alpha (TNF-α) regulates the expression of proinflammatory cytokines and apoptosis in thyroids. miR-155-5p is upregulated in circulating microvesicles in patients with autoimmune thyroiditis. However, the function and molecular mechanisms of TNF-α and miR-155-5p in the initiation and progression of subacute thyroiditis are largely unknown. Herein, we determined serum TNF-α levels in subacute thyroiditis patients and normal healthy controls by ELISA assay. Proliferation and apoptosis of rat thyroid follicle FRTL-5 cells were determined by MTT, TUNEL, and annexin V staining assays. Protein levels and phosphorylation status were assessed by immunoblotting. miR-155-5p expression was determined by the real-time quantitative PCR. Serum TNF-α was significantly upregulated in patients with subacute thyroiditis compared to that in normal healthy controls. In rat thyroid follicle FRTL-5 cells, TNF-α treatment led to a reduction of cell proliferation and an induction of apoptosis. It also increased IL-6 expression and phosphorylation of JAK2 and STAT3. Importantly, we demonstrated that serum miR-155-5p was upregulated in subacute thyroiditis patients and TNF-α stimulated the expression of miR-155-5p in FRTL-5 cells. We found that miR-155-5p inhibited the proliferation and induced apoptosis of FRTL-5 cells and increased the expression of IL-6 in FRTL-5 cells. Our results demonstrated that serum TNF-α and miR-155-5p were upregulated in patients with subacute thyroiditis, and TNF-α inhibited proliferation and induced apoptosis of rat thyroid follicle FRTL-5 cells via modulating the IL-6-JAK2/STAT3 pathway and miR-155-5p signaling. Our findings suggest that miR-155-5p might be a novel biomarker of subacute thyroiditis.