A Novel Role for the Thyroid Hormone-Activating Enzyme Type 2 Deiodinase in the Inflammatory Response of Macrophages

J. Kwakkel, O. V. Surovtseva, E. M. de Vries, J. Stap, E. Fliers, A. Boelen

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Deiodinase type 2 (D2) is a thyroid hormone-activating enzyme converting the prohormone T-4 into the active hormone T-3. In the present study, we show for the first time that D2 is up-regulated in the mouse liver during acute and chronic inflammation, in close correlation with the proinflammatory cytokine IL-1 beta and independently of serum T-3. Inflammation-induced D2 expression was confirmed in macrophages, in conjunction with selective thyroid hormone transporter (monocarboxylate transporter 10) and thyroid hormone receptor (TR)alpha 1 stimulation, and was absent in hepatocytes. Moreover, D2 knockdown in macrophages resulted in a clear attenuation of the lipopolysaccharide (LPS)-induced IL-1 beta and GM-CSF expression, in addition to aberrant phagocytosis. Locally produced T-3, acting via the TR alpha, may be instrumental in this novel inflammatory response, because LPS-treated TR alpha(0/0) mice showed a markedly decreased LPS-induced GM-CSF mRNA expression. We now propose that hepatic D2 favors the innate immune response by specifically regulating cellular thyroid hormone levels in macrophages
Original languageEnglish
Pages (from-to)2725-2734
Issue number7
Publication statusPublished - 2014

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