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TIM4/NLRP3 axis participates in the effects of M1 macrophages on inflammatory factor release, apoptosis and cell adhesion in thyroid follicular cells

  • Authors:
    • Yongjun Cao
    • Yumeng Sun
    • Xiaowen Jin
    • Xiaoqian Li
    • Le Chen
    • Yan Qiu
  • View Affiliations / Copyright

    Affiliations: Department of Endocrinology, Nantong Hospital Affiliated to Nanjing University of Chinese Medicine, Nantong, Jiangsu 226001, P.R. China
    Copyright: © Cao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 679
    |
    Published online on: September 20, 2022
       https://doi.org/10.3892/etm.2022.11615
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Abstract

Hashimoto's thyroiditis (HT) is an autoimmune thyroid disorder that predominantly affects women. The role of the T‑cell immunoglobulin and mucin domain‑containing 4 (TIM4)/ NOD‑, LRR‑ and pyrin domain‑containing protein 3 (NLRP3) signaling pathway in macrophages has previously been studied, but its effects on macrophage‑mediated HT has not yet been reported. Therefore, the aim of the current study was to explore the regulatory role of TIM4/NLRP3 in the effects of M1 macrophages on the inflammation, apoptosis and cell adhesion of thyroid follicular cells. To induce M1 macrophage, 10 ng/ml of LPS and  20 ng/ml IFN‑γ were applied for the administration of THP‑1 cells for 24 h. After induction, the mRNA expressions of M1 macrophage markers were assessed utilizing reverse transcription‑quantitative (RT‑q)PCR. Western blotting and immunofluorescence assay were adopted for the appraisement of inducible nitric oxide synthase. Additionally, the expression levels of TIM4 and NLRP3 before or after transfection were tested using RT‑qPCR and western blotting. The release of inflammatory cytokines (TNF‑α, IL‑1β and IL‑6) were estimated using RT‑qPCR and western blotting was adopted for the estimation of phosphorylated (p)‑p65, p65, I‑κB and p‑I‑κB. Furthermore, the apoptosis level as well as the accompanied proteins was appraised via TUNEL and western blotting. The mRNA and protein expressions of αvβ3 were evaluated employing RT‑qPCR and western blotting. The results demonstrated that TIM4 silencing decreased NLRP3 expression level in M1 macrophages. Moreover, TIM4 silencing in M1 macrophages reduced the expression levels of TNF‑α, IL‑6 and IL‑1β, as well as the phosphorylation levels of p65 and IκB in M1 macrophages co‑cultured with Nthy‑ori 3‑1 cells, whereas NLRP3 overexpression significantly reversed these effects. Furthermore, NLRP3 overexpression reversed the decreased apoptotic rate and cell adhesion of Nthy‑ori 3‑1 cells induced by TIM4 silencing. In summary, the present study demonstrated that TIM4‑silencing alleviated the inflammatory damage, apoptosis and cell adhesion of M1 macrophages co‑cultured with Nthy‑ori 3‑1 cells through downregulation of NLRP3. Therefore, the regulation of M1 macrophages via the TIM4/NLRP3 axis may be a potential therapeutic approach for the treatment of patients with HT.
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Copy and paste a formatted citation
Spandidos Publications style
Cao Y, Sun Y, Jin X, Li X, Chen L and Qiu Y: TIM4/NLRP3 axis participates in the effects of M1 macrophages on inflammatory factor release, apoptosis and cell adhesion in thyroid follicular cells. Exp Ther Med 24: 679, 2022.
APA
Cao, Y., Sun, Y., Jin, X., Li, X., Chen, L., & Qiu, Y. (2022). TIM4/NLRP3 axis participates in the effects of M1 macrophages on inflammatory factor release, apoptosis and cell adhesion in thyroid follicular cells. Experimental and Therapeutic Medicine, 24, 679. https://doi.org/10.3892/etm.2022.11615
MLA
Cao, Y., Sun, Y., Jin, X., Li, X., Chen, L., Qiu, Y."TIM4/NLRP3 axis participates in the effects of M1 macrophages on inflammatory factor release, apoptosis and cell adhesion in thyroid follicular cells". Experimental and Therapeutic Medicine 24.5 (2022): 679.
Chicago
Cao, Y., Sun, Y., Jin, X., Li, X., Chen, L., Qiu, Y."TIM4/NLRP3 axis participates in the effects of M1 macrophages on inflammatory factor release, apoptosis and cell adhesion in thyroid follicular cells". Experimental and Therapeutic Medicine 24, no. 5 (2022): 679. https://doi.org/10.3892/etm.2022.11615
Copy and paste a formatted citation
x
Spandidos Publications style
Cao Y, Sun Y, Jin X, Li X, Chen L and Qiu Y: TIM4/NLRP3 axis participates in the effects of M1 macrophages on inflammatory factor release, apoptosis and cell adhesion in thyroid follicular cells. Exp Ther Med 24: 679, 2022.
APA
Cao, Y., Sun, Y., Jin, X., Li, X., Chen, L., & Qiu, Y. (2022). TIM4/NLRP3 axis participates in the effects of M1 macrophages on inflammatory factor release, apoptosis and cell adhesion in thyroid follicular cells. Experimental and Therapeutic Medicine, 24, 679. https://doi.org/10.3892/etm.2022.11615
MLA
Cao, Y., Sun, Y., Jin, X., Li, X., Chen, L., Qiu, Y."TIM4/NLRP3 axis participates in the effects of M1 macrophages on inflammatory factor release, apoptosis and cell adhesion in thyroid follicular cells". Experimental and Therapeutic Medicine 24.5 (2022): 679.
Chicago
Cao, Y., Sun, Y., Jin, X., Li, X., Chen, L., Qiu, Y."TIM4/NLRP3 axis participates in the effects of M1 macrophages on inflammatory factor release, apoptosis and cell adhesion in thyroid follicular cells". Experimental and Therapeutic Medicine 24, no. 5 (2022): 679. https://doi.org/10.3892/etm.2022.11615
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