title: TSH signaling pathways that regulate MCP-1 in human differentiated adipocytes.
abstract: OBJECTIVE
  Adipose tissue is an extra-thyroidal thyroid-stimulating hormone (TSH) target. Increases in lipolysis and in expression and release of interleukin-6 (IL-6) occur in TSH-stimulated adipocytes, and levels of circulating free fatty acids and IL-6 rise following TSH administration to patients with previous thyroidectomy and radioablation for thyroid cancer. Our first objective was to compare how TSH stimulates protein kinase A (PKA) and inhibitor of κB (IκB) kinase (IKK)-β. Our second objective was to investigate whether TSH induces other cytokines besides IL-6.
  
  
  METHODS
  TSH stimulation of either CHO cells expressing human TSH receptor or human abdominal subcutaneous differentiated adipocytes.
  
  
  RESULTS
  Signaling studies showed TSH increased NADPH oxidase activity, and either diphenyleneiodonium (oxidase inhibitor) or N-acetyl cysteine (scavenger of reactive oxygen species) reduced IKKβ phosphorylation. Phosphorylation of protein kinase C-δ, an upstream regulator of NADPH oxidase, was increased by TSH, and rottlerin (PKCδ inhibitor) reduced TSH-stimulated IKKβ phosphorylation. TSH upregulated monocyte chemoattractant protein-1 (MCP-1) mRNA expression and the release of MCP-1 protein in human abdominal differentiated adipocytes. H89 (PKA inhibitor) and sc-514 (IKKβ inhibitor) each blocked TSH-stimulated MCP-1 mRNA expression and protein release, suggesting PKA and IKKβ participate in this pathway.
  
  
  CONCLUSIONS
  These data provide new information about TSH signaling in human differentiated adipocytes, and add to the evidence that TSH is a pro-inflammatory stimulus of adipocytes.
authors.affiliation: Chronic Disease Program, Ottawa Hospital Research Institute, Departments of Medicine and of Biochemistry, Microbiology & Immunology, University of Ottawa, Ottawa, Ontario, Canada; Chronic Disease Program, Ottawa Hospital Research Institute, Department of Biochemistry, Microbiology & Immunology, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: AnneMarie
authors.initials: A
authors.lastname: Gagnon
authors.affiliation: Chronic Disease Program, Ottawa Hospital Research Institute, Departments of Medicine and of Biochemistry, Microbiology & Immunology, University of Ottawa, Ottawa, Ontario, Canada; Chronic Disease Program, Ottawa Hospital Research Institute, Department of Biochemistry, Microbiology & Immunology, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Melanie L
authors.initials: ML
authors.lastname: Langille
authors.affiliation: Chronic Disease Program, Ottawa Hospital Research Institute, Departments of Medicine and of Biochemistry, Microbiology & Immunology, University of Ottawa, Ottawa, Ontario, Canada; Chronic Disease Program, Ottawa Hospital Research Institute, Department of Biochemistry, Microbiology & Immunology, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Seham
authors.initials: S
authors.lastname: Chaker
authors.affiliation: Chronic Disease Program, Ottawa Hospital Research Institute, Departments of Medicine and of Biochemistry, Microbiology & Immunology, University of Ottawa, Ottawa, Ontario, Canada; Chronic Disease Program, Ottawa Hospital Research Institute, Department of Biochemistry, Microbiology & Immunology, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Tayze T
authors.initials: TT
authors.lastname: Antunes
authors.affiliation: Chronic Disease Program, Ottawa Hospital Research Institute, Departments of Medicine and of Biochemistry, Microbiology & Immunology, University of Ottawa, Ottawa, Ontario, Canada; Chronic Disease Program, Ottawa Hospital Research Institute, Department of Biochemistry, Microbiology & Immunology, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Jason
authors.initials: J
authors.lastname: Durand
authors.affiliation: Chronic Disease Program, Ottawa Hospital Research Institute, Departments of Medicine and of Biochemistry, Microbiology & Immunology, University of Ottawa, Ottawa, Ontario, Canada; Chronic Disease Program, Ottawa Hospital Research Institute, Department of Biochemistry, Microbiology & Immunology, University of Ottawa, Ottawa, Ontario, Canada. Electronic address: asorisky@ohri.ca.
authors.forename: Alexander
authors.initials: A
authors.lastname: Sorisky
mesh_terms: D017667:Adipocytes / Q000378:metabolism*; D000328:Adult; D000818:Animals; D016466:CHO Cells; D002454:Cell Differentiation; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism*; D006224:Cricetinae; D003412:Cricetulus; D017868:Cyclic AMP-Dependent Protein Kinases / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D051550:I-kappa B Kinase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism*; D008066:Lipolysis / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D050507:Subcutaneous Fat, Abdominal / Q000166:cytology*; D013972:Thyrotropin / Q000378:metabolism* / Q000494:pharmacology
chemical_list: C111835:CCL2 protein, human; D018932:Chemokine CCL2; D015850:Interleukin-6; D012333:RNA, Messenger; D013972:Thyrotropin; D051550:I-kappa B Kinase; C496560:IKBKB protein, human; D017868:Cyclic AMP-Dependent Protein Kinases
keywords: Inhibitor of κB kinase-β; Monocyte chemoattractant protein-1; NADPH oxidase; Protein kinase C-δ; Thyroid-stimulating hormone