TY - JOUR
T1 - Role of type 2 deiodinase in response to acute lung injury (ALI) in mice
AU - Barca-Mayo, Olga
AU - Liao, Xiao Hui
AU - DiCosmo, Caterina
AU - Dumitrescu, Alexandra
AU - Moreno-Vinasco, Liliana
AU - Wade, Michael S.
AU - Sammani, Saad
AU - Mirzapoiazova, Tamara
AU - Garcia, Joe G.N.
AU - Refetoff, Samuel
AU - Weissa, Roy E.
PY - 2011/12/6
Y1 - 2011/12/6
N2 - 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.
AB - 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.
KW - Bronchial alveolar lavage
KW - Euthyroid sick
KW - Nonthyroidal illness
KW - Reverse triiodothyronine
KW - Sepsis
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U2 - 10.1073/pnas.1109926108
DO - 10.1073/pnas.1109926108
M3 - Article
C2 - 22065740
AN - SCOPUS:83755178441
SN - 0027-8424
VL - 108
SP - E1321-E1329
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 49
ER -