title: Role of type 2 deiodinase in response to acute lung injury (ALI) in mice.
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) in mice. Mice exposed to VILI recapitulated the serum TH 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 serum TH levels were 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 hypothyroid WT 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.
authors: Department of Medicine, University of Chicago, Chicago, IL 60637, USA.
authors: Olga
authors: O
authors: Barca-Mayo
authors: Xiao-Hui
authors: XH
authors: Liao
authors: Caterina
authors: C
authors: DiCosmo
authors: Alexandra
authors: A
authors: Dumitrescu
authors: Liliana
authors: L
authors: Moreno-Vinasco
authors: Michael S
authors: MS
authors: Wade
authors: Saad
authors: S
authors: Sammani
authors: Tamara
authors: T
authors: Mirzapoiazova
authors: Joe G N
authors: JG
authors: Garcia
authors: Samuel
authors: S
authors: Refetoff
authors: Roy E
authors: RE
authors: Weiss
mesh_terms: D055371:Acute Lung Injury / Q000097:blood / Q000201:enzymology* / Q000235:genetics; D000818:Animals; D018925:Chemokines / Q000235:genetics; D016207:Cytokines / Q000235:genetics; D004789:Enzyme Activation / Q000502:physiology; D015870:Gene Expression / Q000187:drug effects; D005838:Genotype; D007150:Immunohistochemistry; D007453:Iodide Peroxidase / Q000235:genetics / Q000378:metabolism*; D008168:Lung / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013045:Species Specificity; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000097:blood; D014284:Triiodothyronine / Q000097:blood / Q000494:pharmacology; D055397:Ventilator-Induced Lung Injury / Q000097:blood / Q000201:enzymology* / Q000235:genetics; D000097564:Iodothyronine Deiodinase Type II
chemical_list: D018925:Chemokines; D016207:Cytokines; D007453:Iodide Peroxidase; D013972:Thyrotropin; D013974:Thyroxine; D014284:Triiodothyronine; D000097564:Iodothyronine Deiodinase Type II