4 results on '"Tengesdal IW"'
Search Results
2. Interleukin-37 treatment of mice with metabolic syndrome improves insulin sensitivity and reduces pro-inflammatory cytokine production in adipose tissue.
- Author
-
Ballak DB, Li S, Cavalli G, Stahl JL, Tengesdal IW, van Diepen JA, Klück V, Swartzwelter B, Azam T, Tack CJ, Stienstra R, Mandrup-Poulsen T, Seals DR, and Dinarello CA
- Subjects
- Animals, Biomarkers blood, Diet, High-Fat, Glucose Tolerance Test, Humans, Interleukin-1 genetics, Metabolic Syndrome metabolism, Metabolic Syndrome physiopathology, Mice, Mice, Transgenic, Receptors, Interleukin-1 Type I antagonists & inhibitors, Recombinant Proteins genetics, Recombinant Proteins therapeutic use, Adipose Tissue metabolism, Cytokines biosynthesis, Inflammation Mediators metabolism, Insulin Resistance, Interleukin-1 therapeutic use, Metabolic Syndrome drug therapy, Obesity physiopathology
- Abstract
Obesity and the metabolic syndrome are characterized by chronic, low-grade inflammation mainly originating from expanding adipose tissue and resulting in inhibition of insulin signaling and disruption of glycemic control. Transgenic mice expressing human interleukin 37 (IL-37), an anti-inflammatory cytokine of the IL-1 family, are protected against metabolic syndrome when fed a high-fat diet (HFD) containing 45% fat. Here, we examined whether treatment with recombinant IL-37 ameliorates established insulin resistance and obesity-induced inflammation. WT mice were fed a HFD for 22 weeks and then treated daily with IL-37 (1 μg/mouse) during the last 2 weeks. Compared with vehicle only-treated mice, IL-37-treated mice exhibited reduced insulin in the plasma and had significant improvements in glucose tolerance and in insulin content of the islets. The IL-37 treatment also increased the levels of circulating IL-1 receptor antagonist. Cultured adipose tissues revealed that IL-37 treatment significantly decreases spontaneous secretions of IL-1β, tumor necrosis factor α (TNFα), and C X C motif chemokine ligand 1 (CXCL-1). We also fed mice a 60% fat diet with concomitant daily IL-37 for 2 weeks and observed decreased secretion of IL-1β, TNFα, and IL-6 and reduced intracellular levels of IL-1α in the liver and adipose tissue, along with improved plasma glucose clearance. Compared with vehicle treatment, these IL-37-treated mice had no apparent weight gain. In human adipose tissue cultures, the presence of 50 pm IL-37 reduced spontaneous release of TNFα and 50% of lipopolysaccharide-induced TNFα. These findings indicate that IL-37's anti-inflammatory effects can ameliorate established metabolic disturbances during obesity., (© 2018 Ballak et al.)
- Published
- 2018
- Full Text
- View/download PDF
3. MHC class II super-enhancer increases surface expression of HLA-DR and HLA-DQ and affects cytokine production in autoimmune vitiligo.
- Author
-
Cavalli G, Hayashi M, Jin Y, Yorgov D, Santorico SA, Holcomb C, Rastrou M, Erlich H, Tengesdal IW, Dagna L, Neff CP, Palmer BE, Spritz RA, and Dinarello CA
- Subjects
- Enhancer Elements, Genetic, Haplotypes, Humans, Polymorphism, Single Nucleotide, Autoimmune Diseases immunology, Cytokines biosynthesis, HLA-DQ Antigens immunology, HLA-DR Antigens immunology, Histocompatibility Antigens Class II immunology, Vitiligo immunology
- Abstract
Genetic risk for autoimmunity in HLA genes is most often attributed to structural specificity resulting in presentation of self-antigens. Autoimmune vitiligo is strongly associated with the MHC class II region. Here, we fine-map vitiligo MHC class II genetic risk to three SNPs only 47 bp apart, located within a predicted super-enhancer in an intergenic region between HLA-DRB1 and HLA-DQA1, localized by a genome-wide association study of 2,853 Caucasian vitiligo patients. The super-enhancer corresponds to an expression quantitative trait locus for expression of HLA-DR and HLA-DQ RNA; we observed elevated surface expression of HLA-DR (P = 0.008) and HLA-DQ (P = 0.02) on monocytes from healthy subjects homozygous for the high-risk SNP haplotype. Unexpectedly, pathogen-stimulated peripheral blood mononuclear cells from subjects homozygous for the high-risk super-enhancer haplotype exhibited greater increase in production of IFN-γ and IL-1β than cells from subjects homozygous for the low-risk haplotype. Specifically, production of IFN-γ on stimulation of dectin-1, mannose, and Toll-like receptors with Candida albicans and Staphylococcus epidermidis was 2.5- and 2.9-fold higher in high-risk subjects than in low-risk subjects, respectively (P = 0.007 and P = 0.01). Similarly, production of IL-1β was fivefold higher in high-risk subjects than in low-risk subjects (P = 0.02). Increased production of immunostimulatory cytokines in subjects carrying the high-risk haplotype may act as an "adjuvant" during the presentation of autoantigens, tying together genetic variation in the MHC with the development of autoimmunity. This study demonstrates that for risk of autoimmune vitiligo, expression level of HLA class II molecules is as or more important than antigen specificity.
- Published
- 2016
- Full Text
- View/download PDF
4. MHC class II super-enhancer increases surface expression of HLA-DR and HLA-DQ and affects cytokine production in autoimmune vitiligo
- Author
-
Lorenzo Dagna, Richard A. Spritz, Ying Jin, Brent E. Palmer, Henry A. Erlich, Melinda Rastrou, Giulio Cavalli, Daniel Yorgov, Isak W. Tengesdal, Stephanie A. Santorico, Cherie Holcomb, Charles A. Dinarello, C. Preston Neff, Masahiro Hayashi, Cavalli, G, Hayashi, M, Jin, Y, Yorgov, D, Santorico, Sa, Holcomb, C, Rastrou, M, Erlich, H, Tengesdal, Iw, Dagna, Lorenzo, Neff, Cp, Palmer, Be, Spritz, Ra, and Dinarello, Ca
- Subjects
0301 basic medicine ,Vitiligo ,lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4] ,Single-nucleotide polymorphism ,Major histocompatibility complex ,medicine.disease_cause ,Polymorphism, Single Nucleotide ,Autoimmune Diseases ,Autoimmunity ,03 medical and health sciences ,0302 clinical medicine ,HLA-DQ Antigens ,HLA-DQ ,HLA-DR ,medicine ,Humans ,MHC class II ,Multidisciplinary ,biology ,Haplotype ,Histocompatibility Antigens Class II ,HLA-DR Antigens ,Biological Sciences ,medicine.disease ,Enhancer Elements, Genetic ,030104 developmental biology ,Haplotypes ,030220 oncology & carcinogenesis ,Immunology ,biology.protein ,Cytokines - Abstract
Item does not contain fulltext Genetic risk for autoimmunity in HLA genes is most often attributed to structural specificity resulting in presentation of self-antigens. Autoimmune vitiligo is strongly associated with the MHC class II region. Here, we fine-map vitiligo MHC class II genetic risk to three SNPs only 47 bp apart, located within a predicted super-enhancer in an intergenic region between HLA-DRB1 and HLA-DQA1, localized by a genome-wide association study of 2,853 Caucasian vitiligo patients. The super-enhancer corresponds to an expression quantitative trait locus for expression of HLA-DR and HLA-DQ RNA; we observed elevated surface expression of HLA-DR (P = 0.008) and HLA-DQ (P = 0.02) on monocytes from healthy subjects homozygous for the high-risk SNP haplotype. Unexpectedly, pathogen-stimulated peripheral blood mononuclear cells from subjects homozygous for the high-risk super-enhancer haplotype exhibited greater increase in production of IFN-gamma and IL-1beta than cells from subjects homozygous for the low-risk haplotype. Specifically, production of IFN-gamma on stimulation of dectin-1, mannose, and Toll-like receptors with Candida albicans and Staphylococcus epidermidis was 2.5- and 2.9-fold higher in high-risk subjects than in low-risk subjects, respectively (P = 0.007 and P = 0.01). Similarly, production of IL-1beta was fivefold higher in high-risk subjects than in low-risk subjects (P = 0.02). Increased production of immunostimulatory cytokines in subjects carrying the high-risk haplotype may act as an "adjuvant" during the presentation of autoantigens, tying together genetic variation in the MHC with the development of autoimmunity. This study demonstrates that for risk of autoimmune vitiligo, expression level of HLA class II molecules is as or more important than antigen specificity.
- Published
- 2016
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.