The deiodination of thyroid hormones in extrathyroidal tissues plays an important role modulating hormone action. type II deiodinase (DII) converts thyroxine to the active 3,5,3'-triiodothyronine, and rat is expressed brain, pituitary gland, brown adipose tissue (BAT). Complementary DNAs (cDNAs) for types I III deiodinases (DI DIII, respectively) have been isolated shown code selenoproteins. However, information concerning structure mammalian DII remains limited, pattern its expression human...

The type III iodothyronine deiodinase metabolizes the active thyroid hormones thyroxine and 3,5,3’-triiodothyronine to inactive compounds. Recently, we have characterized a Xenopus laevis cDNA (XL-15) that encodes selenoprotein with activity (St. Germain, D. L., Schwartzman, R., Croteau, W., Kanamori, A., Wang, Z., Brown, D., Galton, V. A.(1994) Proc. Natl. Acad. Sci. U. S. A. 91, 7767-7771). Using XL-15 as probe, screened rat neonatal skin library. Among clones isolated was one (rNS43-1)...

Type 3 iodothyronine deiodinase (D3) catalyzes the conversion of T4 and T3 to inactive metabolites. It is highly expressed in placenta thus can regulate circulating fetal thyroid hormone concentrations throughout gestation. We have cloned a 2.1-kb human placental D3 cDNA which encodes 32-kD protein with Km 1.2 nM for 5 deiodination 340 5' reverse T3. The reaction requires DTT not inhibited by 6n-propylthiouracil. quantitated transiently specifically labeling bromoacetyl [125I]T3. Kcat/Km...

The type III iodothyronine 5-deiodinase metabolizes thyroxine and 3,5,3'-triiodothyronine to inactive metabolites by catalyzing the removal of iodine from inner ring. enzyme is expressed in a tissue-specific pattern during particular stages development amphibia, birds, mammals. Recently, PCR-based subtractive hybridization technique has been used isolate cDNAs prepared Xenopus laevis tadpole tail mRNA that represent genes upregulated thyroid hormone metamorphosis. Sequence analysis one these...

Thyroid hormone (TH) is critical for cardiac development and heart function. In disease, TH metabolism abnormal, many biochemical functional alterations mirror hypothyroidism. Although therapy has been advocated treating a clear benefit of yet to be established, possibly because peripheral actions TH. To assess the potential efficacy in type 2 deiodinase (D2), which converts prohormone thyroxine active triiodothyronine (T3), was expressed transiently mouse hearts by using tetracycline...

The role of negative checkpoint regulators (NCRs) in human health and disease cannot be overstated. V-domain Ig-containing Suppressor T-cell Activation (VISTA) is an Ig superfamily protein predominantly expressed within the hematopoietic compartment has been studied for its regulation T cell responses. findings presented this study show that, unlike all other NCRs, VISTA deficiency dramatically impacts on macrophage cytokine chemokine production, as well chemotactic response VISTA-deficient...

While naïve CD4+ T cells have historically been considered a homogenous population, recent studies provided evidence that functional heterogeneity exists within this population. Using single cell RNA sequencing (scRNAseq), we identify five transcriptionally distinct subsets emerge the positive stage in thymus: quiescence cluster (TQ), memory-like (TMEM), TCR reactive (TTCR), an IFN responsive (TIFN), and undifferentiated (TUND). Elevated expression of transcription factors KLF2, Mx1, Nur77...

The iodothyronine deiodinases are a family of selenoproteins that metabolize thyroxine and other thyroid hormones to active inactive metabolites in number tissues including brain. Using primary cultures rat astroglial cells as model system, we demonstrate the mRNA for type II deiodinase (DII) selenoenzyme is rapidly markedly induced by forskolin 8-bromo-cAMP. induction DII activity, however, was significantly impaired culturing selenium-deficient medium 7 days. Under such conditions,...

Abstract Despite immunogenicity, melanoma-specific vaccines have demonstrated minimal clinical efficacy in patients with established disease but enhanced survival when administered the adjuvant setting. Therefore, we hypothesized that organs bearing metastatic-like melanoma may differentially produce T-cell chemotactic proteins over course of tumor development. Using an model lungs, assessed production specific cytokines and chemokines a time growth, correlated chemokine receptor–specific...

Recent molecular cloning studies in mammals and amphibians have demonstrated that the types I, II, III deiodinases constitute a family of selenoproteins critical importance metabolizing T4 to active (i.e. T3) inactive rT3) metabolites. In several tissues teleost fish, various deiodinase processes been described, but structural functional characteristics these enzymes their relationship present higher vertebrates remains uncertain. Using complementary DNA library derived from liver Fundulus...

Abstract Timely and appropriate levels of thyroid hormone (TH) signaling are necessary to ensure normal developmental outcomes in many tissues. Studies using pharmacological models altered TH status have revealed an influence these hormones on testis development size, but little is known about the role endogenous determinants action developing male gonads. Using a genetic approach, we demonstrate that type 3 deiodinase (D3), which inactivates protects tissues from undue action, key factor....

Abstract RIG-I–like receptors (RLR) are cytosolic RNA sensors that signal through the MAVS adaptor to activate IFN responses against viruses. Whether RLR family has broader effects on host immunity other pathogen families remains be fully explored. In this study, we demonstrate MDA5/MAVS signaling was essential for resistance pulmonary Aspergillus fumigatus challenge regulation of antifungal leukocyte in mice. Activation driven by dsRNA from live A. serving as a key vitality-sensing pattern...

The iodothyronine deiodinases are a family of oxidoreductases that catalyze the removal iodide from thyroid hormones. Each three isoforms contain selenocysteine at its active site and several cysteine residues may be important for catalytic activity. Of particular interest in type I deiodinase (D1) is Cys124, which vicinal to position 126, Cys194, has been conserved all identified date. In present studies, we have characterized functional properties C124A, C194A, C124A/C194A D1 mutants, were...

The inactivation of the phenolic ring deiodinases by natural substrates and iodinated contrast agents such as iopanoic acid (IOP) is a principal mechanism regulating peripheral metabolism thyroid hormones. present studies were designed to investigate cellular biochemical mechanisms mediating this effect on type I 5'-deiodinase (5'DI) in rat liver kidney. We reasoned that if requires direct interaction ligand (e.g. IOP) with 5'DI, then should be blocked prior injection 6n-propyl-2-thiouracil...

We used vertical growth phase (VGP) human VMM5 melanoma cells to ask whether the tumor microenvironment could induce matrix metalloproteinase-1 (MMP-1) in vivo, and this induction correlated with metastasis. isolated two clones from parental cells: a low MMP-1 producing clone (C4) high (C9). When these were injected orthotopically (intradermally) into nude mice, both equally tumorigenic produced equivalent abundant amounts of MMP-1. However, tumors C4 displayed different kinetics distinct...

The phenolic (5′ position) and tyrosyl (5 ring deiodinases which catalyze the peripheral metabolism of thyroid hormones have proven difficult to purify characterize biochemically. present studies used Xenopus laevis oocytes as an in vivo translational assay system for detecting quantitating mRNA these enzymes. injection poly(A)+ RNA prepared from a human term placenta induced 5-deiodinase activity oocytes. expressed increased up 96 h after injection, was proportional amount injected,...

While naive CD4+ T cells have historically been considered a homogenous population, recent studies provided evidence that functional heterogeneity exists within this population. Using single cell RNA sequencing (scRNAseq), we identify five transcriptionally distinct subsets emerge the positive stage in thymus: quiescence cluster (TQ), memory-like (TMEM), TCR reactive (TTCR), an IFN responsive (TIFN), and undifferentiated (TUND). Elevated expression of transcription factors KLF2, Mx1, Nur77...

Radiation therapy (RT) has recently demonstrated promise at stimulating an enhanced immune response. The recent success of immunotherapies, such as checkpoint inhibitors, CART cells, and other modulators, affords new opportunities for combination with radiation. aim this study is to evaluate whether what extent blockade VISTA, checkpoint, can potentiate the tumor control ability radiation therapy. Our novel in that it first comparison two VISTA-blocking methods (antibody inhibition genetic...

Introduction: Radiation therapy (RT) has recently demonstrated promise at stimulating an enhanced immune response. The recent success of immunotherapies, such as checkpoint inhibitors, CART cells, and other modulators, affords new opportunities for combination with radiation. Methods: In this study, VISTA, checkpoint, was blocked either by genetic knockout (KO) or inhibitory antibody combined RT in two syngeneic murine cancer models. Selected mRNA, cell infiltration, tumor growth delay were...

ABSTRACT RIG-I like receptors (RLR) are cytosolic RNA sensors that signal through the MAVS adaptor to activate interferon responses against viruses. Whether RLR family has broader effects on host immunity other pathogen families remains be fully explored. Herein we demonstrate MDA5/MAVS signaling was essential for resistance pulmonary Aspergillus fumigatus challenge regulation of antifungal leukocyte in mice. Activation driven by dsRNA from live A. serving as a key vitality-sensing...