Increased circulating interleukin-8 in patients with resistance to thyroid hormone receptor alpha

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van der Spek A. H., Surovtseva O. V., Aan S., Tool A. T. J., van de Geer A., DEMİR K., ...Daha Fazla

ENDOCRINE CONNECTIONS, cilt.6, sa.8, ss.731-740, 2017 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 6 Sayı: 8
  • Basım Tarihi: 2017
  • Doi Numarası: 10.1530/ec-17-0213
  • Dergi Adı: ENDOCRINE CONNECTIONS
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.731-740
  • Anahtar Kelimeler: thyroid hormone receptor alpha, resistance to thyroid hormone, interleukin-8, macrophage, neutrophil, innate immunity, TYPE-3 DEIODINASE, CLINICAL PHENOTYPE, TR-ALPHA, MUTATION, MICE, NEUTROPHILS, GENE, EXPRESSION, CELLS, HYPOTHYROIDISM
  • Dokuz Eylül Üniversitesi Adresli: Evet

Özet

Innate immune cells have recently been identified as novel thyroid hormone (TH) target cells in which intracellular TH levels appear to play an important functional role. The possible involvement of TH receptor alpha (TR alpha), which is the predominant TR in these cells, has not been studied to date. Studies in TR alpha(0/0) mice suggest a role for this receptor in innate immune function. The aim of this study was to determine whether TR alpha affects the human innate immune response. We assessed circulating interleukin-8 concentrations in a cohort of 8 patients with resistance to TH due to a mutation of TR alpha (RTH alpha) and compared these results to healthy controls. In addition, we measured neutrophil and macrophage function in one of these RTHa patients (mutation D211G). Circulating interleukin-8 levels were elevated in 7 out of 8 RTH alpha patients compared to controls. These patients harbor different mutations, suggesting that this is a general feature of the syndrome of RTH alpha. Neutrophil spontaneous apoptosis, bacterial killing, NAPDH oxidase activity and chemotaxis were unaltered in cells derived from the RTH alpha D211G patient. RTH alpha macrophage phagocytosis and cytokine induction after LPS treatment were similar to results from control cells. The D211G mutation did not result in clinically relevant impairment of neutrophil or pro-inflammatory macrophage function. As elevated circulating IL-8 is also observed in hyperthyroidism, this observation could be due to the high-normal to high levels of circulating T-3 found in patients with RTH alpha.