Role of type 2 deiodinase in response to acute lung injury (ALI) in mice

Olga Barca-Mayo, Xiao Hui Liao, Caterina DiCosmo, Alexandra Dumitrescu, Liliana Moreno-Vinasco, Michael S. Wade, Saad Sammani, Tamara Mirzapoiazova, Joe G N Garcia, Samuel Refetoff, Roy E. Weissa*

*Corresponding author for this work

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

Thyroid hormone (TH) metabolism, mediated by deiodinase types 1, 2, and 3 (D1, D2, and D3) is profoundly affected by acute illness.We examined the role of TH metabolism during ventilator-induced lung injury (VILI) inmice.Mice exposed to VILI recapitulated the serumTH findings of acute illness, namely a decrease in 3,5,3′-triiodothyronine (T 3) and thyroid-stimulating hormone and an increase in reverse T 3. Both D2 immunoreactivity and D2 enzymatic activity were increased significantly. D1 and D3 activity did not change. Using D2 knockout (D2KO) mice, we determined whether the increase in D2 was an adaptive response. Although similar changes in serumTH levelswere observed in D2KO and WT mice, D2KO mice exhibited greater susceptibility to VILI than WT mice, as evidenced by poorer alveoli integrity and quantified by lung chemokine and cytokine mRNA induction. These data suggest that an increase in lung D2 is protective against VILI. Similar findings of increased inflammatory markers were found in hypothyroidWT mice exposed to VILI compared with euthyroid mice, indicating that the lungs were functionally hypothyroid. Treatment of D2KO mice with T 3 reversed many of the lung chemokine and cytokine profiles seen in response to VILI, demonstrating a role for T 3 in the treatment of lung injury. We conclude that TH metabolism in the lung is linked to the response to inflammatory injury and speculate that D2 exerts its protective effect by making more TH available to the injured lung tissue.

Original languageEnglish (US)
Pages (from-to)E1321-E1329
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number49
DOIs
StatePublished - Dec 6 2011

Keywords

  • Bronchial alveolar lavage
  • Euthyroid sick
  • Nonthyroidal illness
  • Reverse triiodothyronine
  • Sepsis

ASJC Scopus subject areas

  • General

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    Barca-Mayo, O., Liao, X. H., DiCosmo, C., Dumitrescu, A., Moreno-Vinasco, L., Wade, M. S., Sammani, S., Mirzapoiazova, T., Garcia, J. G. N., Refetoff, S., & Weissa, R. E. (2011). Role of type 2 deiodinase in response to acute lung injury (ALI) in mice. Proceedings of the National Academy of Sciences of the United States of America, 108(49), E1321-E1329. https://doi.org/10.1073/pnas.1109926108