Effects of thyroid-stimulating hormone on adhesion molecules and pro-inflammatory cytokines secretion in human

Attabak Toofani Milani1, Mohammad Hassan Khadem-Ansari1, Yousef Rasmi1

  • 1Department of Biochemistry, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, I.R. Iran.

Insights

Thyroid-stimulating hormone (TSH) showed anti-inflammatory effects by down-regulating tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). However, TSH also increased markers of endothelial dysfunction and leukocyte adhesion, suggesting a complex role in atherosclerosis.

Area of Science:

  • Endocrinology
  • Cardiovascular Biology
  • Cell Biology

Background:

  • Atherosclerosis is a complex arterial disease linked to cardiovascular disorders, with endothelial dysfunction playing a key role.
  • Hypothyroidism and thyroid hormone deficiency are associated with increased cardiovascular risks.
  • Thyroid-stimulating hormone (TSH) effects on endothelial cells in the context of atherosclerosis require further elucidation.

Purpose of the Study:

  • To investigate the impact of TSH on pro-inflammatory cytokines (TNF-α, IL-6), angiogenic factors (VEGF), and adhesion molecules (ICAM-1, E-selectin) in human umbilical vein endothelial cells (HUVECs).
  • To assess the role of TSH in endothelial dysfunction and leukocyte adhesion, critical processes in atherogenesis.

Main Methods:

  • Human umbilical vein endothelial cells (HUVECs) were treated with varying concentrations (1 and 2 μM) of TSH for different durations.
  • Gene and protein expression of ICAM-1, VEGF, and E-selectin were analyzed using real-time PCR and Western blotting.
  • Protein levels of TNF-α and IL-6 were quantified using ELISA.

Main Results:

  • TSH treatment led to the downregulation of pro-inflammatory cytokines TNF-α and IL-6.
  • Conversely, TSH significantly upregulated the expression of ICAM-1, E-selectin, and VEGF, indicating increased leukocyte adhesion and angiogenesis.
  • These markers of endothelial dysfunction and angiogenic potential were elevated in TSH-treated HUVECs.

Conclusions:

  • TSH exhibits a dual role in atherogenesis: it possesses anti-inflammatory properties but also promotes pathways involved in angiogenesis and leukocyte adhesion.
  • The findings suggest that TSH influences vascular cell proliferation and adhesion, contributing to the complex pathophysiology of atherosclerosis.
  • Further research is warranted to fully understand the implications of TSH's multifaceted actions in the context of vascular disease.

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