A Novel Role for the Thyroid Hormone-Activating Enzyme Type 2 Deiodinase in the Inflammatory Response of Macrophages
| Autor: | Ellen A. Fliers, Olga V. Surovtseva, Anita Boelen, J. Stap, E. M. de Vries, Joan Kwakkel |
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| Přispěvatelé: | Endocrinology Laboratory, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, General Internal Medicine, CCA -Cancer Center Amsterdam, Cell Biology and Histology, ANS - Amsterdam Neuroscience, Endocrinology |
| Rok vydání: | 2014 |
| Předmět: |
Lipopolysaccharides
Male Thyroid Hormones medicine.medical_specialty Mice 129 Strain medicine.medical_treatment Interleukin-1beta Deiodinase Gene Expression Inflammation Biology Iodide Peroxidase Cell Line Proinflammatory cytokine Thyroid hormone receptor beta Mice Endocrinology Cell Line Tumor Internal medicine medicine Animals Humans Mice Knockout Thyroid hormone receptor Reverse Transcriptase Polymerase Chain Reaction Macrophages Thyroid Granulocyte-Macrophage Colony-Stimulating Factor Hep G2 Cells Mice Inbred C57BL Cytokine medicine.anatomical_structure Liver biology.protein Triiodothyronine Female RNA Interference medicine.symptom Thyroid Hormone Receptors alpha Hormone |
| Zdroj: | Endocrinology, 155(7), 2725-2734. The Endocrine Society |
| ISSN: | 1945-7170 0013-7227 |
| Popis: | 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 |
| Databáze: | OpenAIRE |
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