title: Inflammation-inducible type 2 deiodinase expression in the leptomeninges, choroid plexus, and at brain blood vessels in male rodents.
abstract: Thyroid hormone regulates immune functions and has antiinflammatory effects. In promoter assays, the thyroid hormone-activating enzyme, type 2 deiodinase (D2), is highly inducible by the inflammatory transcription factor nuclear factor-κ B (NF-κB), but it is unknown whether D2 is induced in a similar fashion in vivo during inflammation. We first reexamined the effect of bacterial lipopolysaccharide (LPS) on D2 expression and NF-κB activation in the rat and mouse brain using in situ hybridization. In rats, LPS induced very robust D2 expression in normally non-D2-expressing cells in the leptomeninges, adjacent brain blood vessels, and the choroid plexus. These cells were vimentin-positive fibroblasts and expressed the NF-κB activation marker, inhibitor κ B-α mRNA, at 2 hours after injection, before the increase in D2 mRNA. In mice, LPS induced intense D2 expression in the choroid plexus but not in leptomeninges, with an early expression peak at 2 hours. Moderate D2 expression along numerous brain blood vessels appeared later. D2 and NF-κB activation was induced in tanycytes in both species but with a different time course. Enzymatic assays from leptomeningeal and choroid plexus samples revealed exceptionally high D2 activity in LPS-treated rats and Syrian hamsters and moderate but significant increases in mice. These data demonstrate the cell type-specific, highly inducible nature of D2 expression by inflammation, and NF-κB as a possible initiating factor, but also warrant attention for species differences. The results suggest that D2-mediated T₃ production by fibroblasts regulate local inflammatory actions in the leptomeninges, choroid plexus and brain blood vessels, and perhaps also in other organs.
authors.affiliation: Department of Medicine (G.W., P.S.S., S.S.N., R.M.L.), Division of Endocrinology, Diabetes and Metabolism, Tupper Research Institute, Tufts Medical Center, and Department of Neuroscience (R.M.L.), Tufts University School of Medicine, Boston, Massachusetts 02111; Thyroid Section (J.W.H., P.R.L.), Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital, Boston, Massachusetts 02115; and School of Biological Sciences (P.S.S.), National Institute of Science Education and Research, Institute of Physics Campus, PO Sainik School, Bhubaneswar-751005, India.
authors.forename: Gábor
authors.initials: G
authors.lastname: Wittmann
authors.forename: John W
authors.initials: JW
authors.lastname: Harney
authors.forename: Praful S
authors.initials: PS
authors.lastname: Singru
authors.forename: Shira S
authors.initials: SS
authors.lastname: Nouriel
authors.forename: P
authors.initials: P
authors.lastname: Reed Larsen
authors.forename: Ronald M
authors.initials: RM
authors.lastname: Lechan
mesh_terms: D000818:Animals; D001099:Arachnoid / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000098:blood supply / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002831:Choroid Plexus / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D006224:Cricetinae; D004195:Disease Models, Animal; D004660:Encephalitis / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D004790:Enzyme Induction; D063928:Ependymoglial Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D007453:Iodide Peroxidase / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D008297:Male; D008578:Meninges / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008581:Meningitis / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008647:Mesocricetus; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D010841:Pia Mater / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D000097564:Iodothyronine Deiodinase Type II
chemical_list: D007453:Iodide Peroxidase; D016328:NF-kappa B; D009419:Nerve Tissue Proteins; D000097564:Iodothyronine Deiodinase Type II